Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.
Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A cell line derived from cultured tumor cells.
Established cell cultures that have the potential to propagate indefinitely.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
Signal molecules that are involved in the control of cell growth and differentiation.
A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Agents that inhibit PROTEIN KINASES.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A family of closely related RECEPTOR PROTEIN-TYROSINE KINASES that bind vascular endothelial growth factors. They share a cluster of seven extracellular Ig-like domains which are important for ligand binding. They are highly expressed in vascular endothelial cells and are critical for the physiological and pathological growth, development and maintenance of blood and lymphatic vessels.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).
Tumors or cancer of the LUNG.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Proteins prepared by recombinant DNA technology.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Antibodies produced by a single clone of cells.
Tumors or cancer of the human BREAST.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.
A fibroblast growth factor that is a specific mitogen for EPITHELIAL CELLS. It binds a complex of HEPARAN SULFATE and FIBROBLAST GROWTH FACTOR RECEPTOR 2B.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A 17-kDa single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. It binds to HEPARIN, which potentiates its biological activity and protects it from proteolysis. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages, and also has chemotactic and mitogenic activities. It was originally named acidic fibroblast growth factor based upon its chemical properties and to distinguish it from basic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 2).
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
The proto-oncogene c-erbB-1 codes for the epidermal growth factor receptor. Its name originates from the viral homolog v-erbB which was isolated from an avian erythroblastosis virus (AEV) where it was contained as a fragment of the chicken c-ErbB-1 gene lacking the amino-terminal ligand-binding domain. Overexpression of erbB-1 genes occurs in a wide range of tumors, commonly squamous carcinomas of various sites and less commonly adenocarcinomas. The human c-erbB-1 gene is located in the chromosomal region 7p14 and 7p12.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A 200-230-kDa tyrosine kinase receptor for vascular endothelial growth factors found primarily in endothelial and hematopoietic cells and their precursors. VEGFR-2 is important for vascular and hematopoietic development, and mediates almost all endothelial cell responses to VEGF.
NERVE GROWTH FACTOR is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Elements of limited time intervals, contributing to particular results or situations.
A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Repair or renewal of hepatic tissue.
A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
The rate dynamics in chemical or physical systems.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.
A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
A fibroblast growth factor that is a mitogen for KERATINOCYTES. It activates FIBROBLAST GROWTH FACTOR RECEPTOR 2B and is involved in LUNG and limb development.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
Restoration of integrity to traumatized tissue.
A PDGF receptor that binds specifically to both PDGF-A chains and PDGF-B chains. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
A 180-kDa VEGF receptor found primarily in endothelial cells that is essential for vasculogenesis and vascular maintenance. It is also known as Flt-1 (fms-like tyrosine kinase receptor-1). A soluble, alternatively spliced isoform of the receptor may serve as a binding protein that regulates the availability of various ligands for VEGF receptor binding and signal transduction.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A malignant epithelial tumor with a glandular organization.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Peptides and proteins found in BODILY SECRETIONS and BODY FLUIDS that are PROTEASE INHIBITORS. They play a role in INFLAMMATION, tissue repair and innate immunity (IMMUNITY, INNATE) by inhibiting endogenous proteinases such as those produced by LEUKOCYTES and exogenous proteases such as those produced by invading microorganisms.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Mode of communication wherein a bound hormone affects the function of the cell type that produced the hormone.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Adherence of cells to surfaces or to other cells.
Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Transplantation between animals of different species.
A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It is found in hypertrophic CHONDROCYTES where it may play a role in CHONDROGENESIS and endochondral ossification.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The action of a drug in promoting or enhancing the effectiveness of another drug.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.
A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
A low affinity receptor that binds NERVE GROWTH FACTOR; BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN 3; and neurotrophin 4.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.
Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
A fibroblast growth factor receptor that is mainly expressed in LUNG; KIDNEY; PANCREAS; and SPLEEN. It also plays an important role in SKELETAL MUSCLE development and can contribute to NEOPLASTIC CELL TRANSFORMATION.
Cellular DNA-binding proteins encoded by the sis gene (GENES, SIS). c-sis proteins make up the B chain of PLATELET-DERIVED GROWTH FACTOR. Overexpression of c-sis causes tumorigenesis.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Other growth factors had no inductive effect except for a slight effect of epidermal growth factor treatment. Sema3A ... when treated with hepatocyte growth factor (HGF), established as an essential cue in muscle fiber growth and regeneration. When ... of the cells. Neutralizing antibody to the HGF-specific receptor, c-met, did not abolish the HGF response, indicating that c- ... Other growth factors had no inductive effect except for a slight effect of epidermal growth factor treatment. Sema3A ...
... fibroblast growth factor, FGF; hepatocyte growth factor, HGF; epidermal growth factor, EGF; insulin-like growth factor 1, IGF1 ... Cells Tissues Organs. 2007;185(1-3):123-30.. *Zhang L, et al. Signaling interplay between transforming growth factor-B receptor ... transmembrane receptors controlling cell-cell and cell-matrix adhesion) [46] are all upregulated in cells that have undergone ... Although most of these growth factors have roles in inducing EMT during normal development, these growth factors can also lead ...
... the response of the retinal pigment epithelium to basic fibroblast growth factor and epidermal growth factor by receptor ... HGF (hepatocyte growth factor) increases susceptibility of epithelial cells to pseudomonas aeruginosa virulence mechanisms. 38 ... The effect of growth factors and conditioned media on the proliferation of human corneal epithelial cells and keratocytes. 37. ... Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses.. 53:2030-2037. 2012 ...
... and TGF-β kinase inhibitor LY2109761 treated Hep G2 cell lines have been investigated. ... the impact of Transforming growth factor beta (TGF-β) ... the Effect of Targeting the Epidermal Growth Factor Receptor on ... cells carries a huge amount of cellular functions like general hepatocytes such as hepatocyte-specific cell surface receptors ... extracellular and cell surface proteins involved in cell-cell and cell-flask attachment thus releasing cells into suspension. ...
Secretion By Cell. *Epidermal Growth Factor Receptor Signaling Pathway. *Negative Regulation Of Transforming Growth Factor Beta ... hepatocyte growth factor-regulated tyrosine kinase substrate. Image. No pdb structure. Gene Ontology Annotations. Cellular ... Negative Regulation Of Cellular Response To Growth Factor Stimulus. *Ubiquitin-dependent Protein Catabolic Process Via The ... Epidermal Growth Factor Receptor Signaling Pathway. *Negative Regulation Of Cell Proliferation. *Endosome To Lysosome Transport ...
Epidermal Growth Factor Receptor in Macrophages Mediates Feedback Inhibition of M2 Polarization and Gastrointestinal Tumor Cell ... The recycling of apolipoprotein E in primary cultures of mouse hepatocytes. Evidence for a physiologic connection to high ... Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages.. Orr JS, Puglisi MJ, ... Crystallization of free cholesterol in model macrophage foam cells.. Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP ...
Glutamine is essential for epidermal growth factor-stimulated intestinal cell proliferation.. Ko TC, Beauchamp RD, Townsend CM ... Proglumide, a gastrin receptor antagonist, inhibits growth of colon cancer and enhances survival in mice.. Beauchamp RD, ... The capacity of the malate-aspartate shuttle differs between periportal and perivenous hepatocytes from rats.. Shiota M, ... 2012) Cell Metab 15: 110-21. *Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell ...
document titled Hepatocellular Carcinoma Stem Cells: Origins and Roles in Hepatocarcinogenesis and is about Biotechnology ... hepatocyte growth factor (HGF), heparin. -. binding epidermal growth factor. -. like growth. factor,. epidermal growth factor, ... factor; VEGFR, VEGF receptor; EGF, epidermal growth factor; EGFR, EGF receptor; IGF. -. 1R,. insulin. -. like. growth factor. - ... PDGF), transforming growth factor (TGF). -. α and β, and basic fibroblast growth factors (FGF). (120). . These growth factors ...
A POI mouse model was established and human ovarian granule cells (hGCs) collected from individuals with POI were prepared to ... These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism ... We designed this experimental study to investigate whether human adipose stem cell-derived exosomes (hADSC-Exos) retain the ... The proliferation rate and marker expression levels of hGCs were measured by flow cytometry (fluorescence-activated cell ...
The other growth factors are EGFs (Epidermal Growth Factors), PDGFs (Platelet-Derived Growth Factors), FGFs (Fibroblast Growth ... Factors), VEGFs (Vascular Endothelial Growth Factors), IGFs (Insulin-like Growth Factors), HGFs (Hepatocyte Growth Factors), ... This factor has prompted research entities to go for 3D cell culture techniques. These days, 3D tissue-engineered models are ... has a hydromorphone hydrochloride injection called "Naruvein Injection". GlaxoSmithKline develops a neurokinin 1 receptor ...
Single molecule imaging of the signaling activity of the epidermal growth factor receptor. Bastiaens, Philippe I.; Ibach, Jenny ... Gene networks and transcription factor motifs defining the differentiation of human embryonic stem cells into hepatocyte like ... The cytosolic state of the integrin adhesome and its relation with cell matrix adhesion sites. Zamir, Eli; Hoffmann, Jan-Erik; ... Interference with the spatial organization of Ras in cancer cells. Bastiaens, Philippe; Truxius, Dina Carolin; Wehner, Frank. ...
5 Harshman, L., and Choueiri, T. Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer ... growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor ... OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some ... Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell ...
... reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell ... Plasma hepatocyte growth factor (HGF) concentration was determined using quantitative sandwich enzyme immunoassay technique ( ... Among ErbB receptors, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have been ... A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 ...
H1 Receptors Background: Epidermal growth element receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including ... and hepatocyte nuclear factor 4mice and lowers blood glucose (69). Thus, perhaps disinhibition of glucagons normal effects on ... H1 Receptors Although this process fails in 10C50%13,14,28 and a CNA profile cant be obtained for each cell, we discovered ... Background: Epidermal growth element receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and ...
The kinetics of tyrosine phosphorylation by the purified epidermal growth factor receptor kinase of A-431 cells. J Biol Chem ... modulates Ca2+ responses in rat hepatocytes FASEB J 2007 21, 1481-1491. ... J Cell Sci. 2018 Aug 16;131(16).. 12. The impact of phosphoinositide 5-phosphatases on phosphoinositides in cell function and ... Inhibition of SHIP2 activity inhibits cell migration and could prevent metastasis in breast cancer cells", Somadri Ghosh, ...
Hepatocyte Growth Factor Receptors *Her *hERG Channels *Hexokinase *Hexosaminidase, Beta *HGFR *Hh Signaling ... miR-191 phrase is upregulated in senescencent human epidermal keratinocytes. pores and skin can be a cells with a high turnover ... miR-191 phrase is upregulated in senescencent human epidermal keratinocytes. pores. February 7, 2018. Billie Young ... In the present study, we proven that vanillin ameliorates the doxo-induced toxicity in H9c2 cells significantly ...
... is often used while first-line targeted therapy in adenocarcinoma of the lung with epidermal growth element receptor (EGFR) ... on undesirable event information of epidermal development aspect receptor-tyrosine kinase inhibitors in nonsmall cell lung ... Lack of Tpl2 in hepatocytes suppressed IL-25-induced chemokine CXCL1/2 appearance, which impaired the recruitment of MDSC in to ... Mistake bars represent regular deviations, factor after College students 0.01. Phylogenetic evaluation of BIG subfamily ...
... where additional factors, including receptor and ligand densities, might influence cell-cell interactions and NK education. ... ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor ... human being epidermal development receptor, revised radical mastectomy, mastectomy, sentinel lymph node biopsy, triple-negative ... Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, ...
... by a mouse gamma delta T cell receptor.. Ito K, Van Kaer L, Bonneville M, Hsu S, Murphy DB, Tonegawa S. (1990) Cell 62: 549-61 ... A new type of transforming growth factor-beta, TGF-beta 3.. Derynck R, Lindquist PB, Lee A, Wen D, Tamm J, Graycar JL, Rhee L, ... No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients ... Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3.. de Guzman Strong C, ...
CD34 cells are isolated from the UCB cells and through the combination of fibroblast growth factor and hepatocyte growth factor ... with extracellular domain that contain 10 epidermal growth factor and it is responsible for adhesion or ligand receptor ... The cultured system with growth factors have the ability to convert these UCB cells into hepatocytes phenotype and it is ... cells from the UCB cells can be converted into hepatic-like cells under suitable conditions with appropriate growth factors. ...
CD34 cells are isolated from the UCB cells and through the combination of fibroblast growth factor and hepatocyte growth factor ... with extracellular domain that contain 10 epidermal growth factor and it is responsible for adhesion or ligand receptor ... The cultured system with growth factors have the ability to convert these UCB cells into hepatocytes phenotype and it is ... cells from the UCB cells can be converted into hepatic-like cells under suitable conditions with appropriate growth factors. ...
Epidermal Growth Factor Receptor (EGFR) genotyping is critical for treatment guideline such as the use of tyrosine kinase ... We quantified 21,950 mRNAs and 8297 proteins in HCV-infected cells. Upon HCV infection of hepatocyte-like cells and chimeric ... A CT-based radiomics nomogram for prediction of human epidermal growth factor receptor 2 status in patients with gastric cancer ... CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of ...
Stem Cells 59% * Oligodendroglia 53% * Epidermal Growth Factor 31% * NIEMANN-PICK DISEASE. Wasserstein, M. P. ... P27Kip1 in Hepatocyte Proliferation. Zhu, L.. 9/1/02 → 6/30/07 ... Interleukin 1 Receptor Antagonist Protein 30% * Genetic ... Peripheral blood B cells in systemic lupus erythematosus. Porcelli, S. A., Putterman, C., Diamond, B. & Davidson, A. ... Beta cell insulin granule docking, priming and fusion. Pessin, J. E. & Rose, S. A. ...
Epidermal growth factor (EGF) and hormones stimulate phosphoinositide hydrolysis and increase EGF receptor protein synthesis ... smooth muscle cells and hepatocytes), accessory (glial cells, astrocytes and Muller cells) and immune (antigen presenting cells ... What produces nerve growth factor?. NGF is produced and utilized by several cell types, including structural (epithelial cells ... Who discovered nerve growth factor?. Rita Levi-MontalciniThe discovery of nerve growth factor (NGF) by Rita Levi-Montalcini in ...
Epidermal Growth Factor Receptor Signaling Pathway. *ERBB Signaling Pathway. *Fibroblast Growth Factor Receptor Signaling ... Response To Growth Factor. *Phosphatidylinositol-mediated Signaling. *Immune Response-regulating Cell Surface Receptor ... Hepatocyte Apoptotic Process. *Negative Regulation Of Fibroblast Apoptotic Process. *DNA Damage Checkpoint ... Epidermal Growth Factor Receptor Signaling Pathway. *Regulation Of Phosphorus Metabolic Process. *Regulation Of Kinase Activity ...
... an inhibitory antibody to Human being epidermal growth element receptor 2 [HER2]) resistance which poses a serious problem ... Platelet-Activating Factor (PAF) Receptors Recent Posts. * Target probe sets (1:40 in Probe Set Diluent QT) designed against ... RNAs and proteins SU 3327 in the HCC-derived exosomes will vary from those in the exosomes produced from regular hepatocytes. ... CXCR5+Foxp3? cells had been thought as Tfh cells, while CXCR5+Foxp3+ Rabbit Polyclonal to IRF-3 (phospho-Ser386) cells had been ...
It is currently approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative ... Background and Purpose Targeting macrophage but not hepatocyte liver X receptors (LXRs) can reduce atherosclerosis without ... International Journal of Biochemistry and Cell Biology (3) * International Journal of Machine Learning and Cybernetics (3) ... Targeting macrophage liver X receptors by hydrogel‐encapsulated T0901317 reduces atherosclerosis without effect on hepatic ...
... and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K→ ... By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated ... Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These ... These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant ...
Modulation of human corneal stromal cell differentiation by hepatocyte growth factor and substratum compliance. Exp Eye Res. ... Effect of topical administration of epidermal growth factor on healing of corneal epithelial defects in horses. Am J Vet Res. ... Using Liquid Crystals to Amplify Protein-Receptor Interactions: Design of Surfaces with Nanometer-Scale Topography that Present ... The role of hepatocyte growth factor in corneal wound healing. Exp Eye Res. 2018 01; 166:49-55. Miyagi H, Thomasy SM, Russell P ...
Furthermore, we demonstrated that WT1pos cells uniquely secreted hepatocyte growth factor (HGF) as a key antiapoptotic factor ... The WT1pos cells formed colony-like aggregates in culture that subsequently generated phase-bright cells that homogenously ... tumor factor 1 (WT1) as a key hallmark of fetal reprograming in the pericardial adipose-derived stem cells (pADSC). We ... Remarkably, cardiac transplantation of WT1pos cells promoted regional angiogenesis and myogenesis which led to significant ...
  • Despite the lack of response to L2G7 or erlotinib as single agents, their combination synergized to produce substantial antitumor effects (inhibited tumor cell proliferation, enhanced apoptosis, arrested tumor growth, prolonged animal survival), against subcutaneous and orthotopic U87-EGFRvIII xenografts. (
  • WA inhibits cell proliferation of uveal melanoma cells with an IC50 of 0.90, 1.66, and 2.42 μM for OMM2.3, 92.1, and MEL290 cells, respectively. (
  • Our observation indicates that WA is a potent drug that inhibits cell proliferation, shifts cell cycle arrest, and induces apoptosis in multiple UM cell lines in vitro. (
  • Calipel A, Mouriaux F, Glotin AL, Malecaze F, Faussat AM, Mascarelli F. Extracellular signal-regulated kinase-dependent proliferation is mediated through the protein kinase A/B-Raf pathway in human uveal melanoma cells. (
  • Epidermal growth factor (EGF) is important in the regulation of proliferation in hepatocytes. (
  • HT lymphoblasts displayed enhanced [Ca 2+ ] i increases, IP 3 formation, and proliferation upon stimulation with platelet-activating factor and somatostatin. (
  • Combined genetic alterations in these factors result in aggressive cellular proliferation, invasion, and angiogenesis rendering malignant gliomas resistant to intensive therapy. (
  • An in vitro model of wound healing was used to study cell migration that is independent of proliferation during renal regeneration after acute tubular necrosis. (
  • Proteins of the transforming growth factor beta family (TGFβ) are involved in the regulation of proliferation, differentiation, migration and adhesion of most cell types. (
  • TGFβ 1 , which represents the best-studied member of this family, inhibits the proliferation and induces differentiation of epithelial cells ( Attisano and Wrana, 2002 ). (
  • Using C6 cells as a model, here we demonstrate that NHE5 has an important role in tumor growth and tumor cell proliferation and invasion. (
  • Although previous studies showed the importance of NHE1 in cell proliferation [ 7 , 8 , 9 , 10 ], little is known about the involvement of other NHE isoforms that may be expressed in malignant tumor cells. (
  • In the current study, we have investigated the involvement of NHE5 and NHE1 in glioma cell signaling, proliferation, and tumor growth through characterization of C6 glioma-based knockdown cell lines. (
  • In this regard, we measured ulcer size, mucus thickness, epithelial cell proliferation and apoptosis, and angiogenesis at the ulcer site at different time points after ulcer induction. (
  • It also decreased mucus content and epithelial cell proliferation at the ulcer margin as well as angiogenesis at the ulcer margin and base. (
  • Thus, it is interesting to investigate whether a non-ulcerogenic dose of corticosteroid could indeed affect cell proliferation, angiogenesis, and apoptosis at the ulcer site during ulcer healing. (
  • In this study, ascorbic acid (1-3 mM) decreased RKO and SW480 colon cancer cell proliferation and induced apoptosis and necrosis, and this was accompanied by downregulation of Sp1, Sp3, and Sp4 proteins. (
  • Subsequently, IL-6 is produced in Kupffer cells by the activation of NF-κB and stimulates janus kinase (JAK)/signal transduction and activator of transcription (STAT) by binding to its receptor (IL-6R) in hepatocytes, resulting in hepatocyte proliferation ( 4 - 6 ). (
  • As a cell surface protein that binds to epidermal growth factor, its binding to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation, of which altered activity has been implicated in the development and growth of many tumors [ 3 ]. (
  • Mice lacking EGFR or heparin-binding EGF show delayed regeneration after partial hepatectomy (PH), which demonstrates that EGFR is a critical regulator of hepatocyte proliferation during liver regeneration [ 6 , 7 ]. (
  • Knockdown of c-Met decreased proliferation of high c-Met-expressing UM cells but did not induce apoptosis. (
  • Selective inhibitors of EGFR and IGF-1R decreased proliferation and induced apoptosis in UM cells regardless of the expression levels of c-Met, EGFR, and IGF-1R. (
  • The HER family of receptors consists of four members-ErbB-1 (HER1 or epidermal growth factor receptor [EGFR]), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-that share a common structure and regulate cell proliferation, differentiation, and apoptosis when activated to form homoand heterodimers that facilitate signal transduction [6,7]. (
  • hADSCs isolated from 61 women of different ages were cultured for evaluation of the proliferation of cells, adherence, apoptosis, immunomodulation, immunophenotyping, multipotency, gene expression, and cell function during Hep-Dif. (
  • the low potentials of cell proliferation, doubling, adherence, and immunomodulatory ability (proinflammatory over anti-inflammatory) contrary to the apoptotic index of the aged group were significantly reversed by ML141. (
  • Recent strategies in tissue engineering and cell therapy have shown the efficacies of human adipose-derived MSCs (hADSCs) in regenerative medicine [ 7 ] and that hADSCs hold numerous benefits over bone marrow-derived MSCs (BMSCs) with higher potentials for proliferation and differentiation capacities in vitro [ 8 ]. (
  • Lemur tyrosine kinase 2 acts as a positive regulator of NF-κB activation and colon cancer cell proliferation. (
  • cell proliferation. (
  • We found that LMTK2 protein was abundant in colon cancer cells and LMTK2 knockdown (LMTK2-KD) inhibited proliferation of colon cancer cells through inactivating NF-κB. (
  • Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation. (
  • involved with inhibiting cell proliferation in response to taxol. (
  • The aim of this research project was to study the effect of DNOP on the proliferation of normal mouse hepatocytes and the growth factor implicated. (
  • The rate of cell proliferation of AML-12 cells was measured using MTT cell proliferation assay kit. (
  • The rate of cell proliferation increased in those cells treated with 0.1% DNOP at 72 h and 96 h. (
  • Kinases regulate many different cell proliferation, differentiation, and signaling processes by adding phosphate groups to proteins. (
  • HGF-MET signaling directs the proliferation and migration of epithelial cells during the development of various organs and is important during wound healing. (
  • The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. (
  • Effect of transforming growth factor-beta1 and -beta2 on in vitro rabbit corneal epithelial cell proliferation promoted by epidermal growth factor, keratinocyte growth factor, or hepatocyte growth factor. (
  • Addition of pro-HGF-secreting conditioned fibroblast media to TNBC cells as well as co-culturing of TNBC cells with RMF-HGF fibroblasts resulted in robust phosphorylation of Met and stimulated proliferation in the presence of an EGFR TKI. (
  • on collagen synthesis and cell proliferation in human stellate cells from pancreatic head adenocarcinoma. (
  • Sema3A upregulation was HGF dose dependent with a maximum (about 7- to 8-fold units relative to the control) at 10-25 ng/ml and occurred exclusively at the early-differentiation stage, as characterized by the level of myogenin expression and proliferation (bromodeoxyuridine incorporation) of the cells. (
  • In addition, HGF (5 ng/ml), and EGF (10 ng/ml) were found to stimulate HTM cell proliferation in low serum media but there was no significant proliferate effect with KGF. (
  • We also show that HGF and EGF stimulate proliferation of HTM cells. (
  • It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-beta. (
  • An EGF/TGF-alpha-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-beta may serve to limit hepatocyte proliferation. (
  • Recent advances in molecular biology have led to the identification of new molecular targets, such as epidermal growth factor receptor ( EGFR ) mutations and echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene, in lung cancer. (
  • For example, hepatocyte growth factor (HGF), the ligand of a tyrosine kinase receptor Met, activates Met and the downstream PI3K/Akt pathway and triggers resistance to EGFR inhibitors in EGFR mutant lung cancer cells. (
  • Moreover, EGFR ligands activate EGFR and downstream pathways and trigger resistance to crizotinib in EML4-ALK lung cancer cells. (
  • Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. (
  • Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR -activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. (
  • Strong immunoreactivity for HGF in cancer cells was detected in lung adenocarcinoma patients harboring EGFR -activating mutations, but no T790M mutation or MET amplification, who showed intrinsic or acquired resistance to gefitinib. (
  • Receptor tyrosine kinase (RTK) systems, such as hepatocyte growth factor (HGF) and its receptor c-Met, and epidermal growth factor receptor (EGFR), are responsible for the malignant progression of multiple solid tumors. (
  • This study investigates how EGFRvIII, a constitutively active EGFR deletion mutant, alters tumor growth and signaling responses to RTK inhibition in PTEN-null/HGF + /c-Met + glioma xenografts. (
  • Osimertinib has been demonstrated to overcome the epidermal growth factor receptor (EGFR)-T790M, the most relevant acquired resistance to first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). (
  • Non-small-cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-activating mutation accounts for ~30-40% of NSCLC in the Japanese population and ~15% in Caucasians 1 . (
  • In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after previous treatment will be enrolled and receive JNJ-61186372 at the RP2D determined in Part 1 as a monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD regimen. (
  • These include epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), and their specific receptors (EGFR, PDGFR, and IGFR), all of which are involved in autocrine or paracrine signaling in gliomas [ 3 - 7 ]. (
  • The defect is accompanied by a strong reduction or absence of several growth factor receptor tyrosine kinases (RTKs) like epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-met) and ERBB3. (
  • Purpose:Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant lung cancer cells by activating Met and the downstream PI3K/Akt pathway. (
  • Experimental Design:The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR-mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion, and H1975 with an T790M secondary mutation. (
  • Results:E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. (
  • Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). (
  • Here, we report for the first time that bivalent Smac mimetic Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells, two patient tumor-derived IBC models. (
  • 18 α -GAMG was firstly nicely bound to epidermal growth factor receptor (EGFR) via six hydrogen bonds and one charge interaction, and the docking calculation proved the correlation between anticancer activities and EGFR inhibitory activities. (
  • The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that defines a family of tyrosine kinase receptors (TKRs) including ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4 [ 1 , 2 ]. (
  • EGFR is highly expressed in adult hepatocytes and the EGFR family plays a central hepatoprotective and pro-regenerative role in the liver [ 4 , 5 ]. (
  • The treatment of hepatocellular carcinoma (HCC) cells with EGFR-specific tyrosine kinase inhibitors or neutralizing antibodies induces cell cycle arrest and apoptosis and increases chemosensitivity [ 8 , 9 ]. (
  • UM cell lines were evaluated for c-Met, epidermal growth factor receptor (EGFR), and insulin-like growth factor-1R (IGF-1R) expression by immunoblotting, and gene amplification by comparative genomic hybridization and fluorescence in-situ hybridization. (
  • High c-Met, phosphorylated c-Met, and EGFR expression were noted in two of nine cell lines, independent of IGF-1R levels. (
  • Although c-Met, EGFR, and IGF-1R play proliferative roles, EGFR and IGF-1R are also critical for UM cell survival. (
  • High c-Met/EGFR-expressing cell lines possessed the greatest migration potential. (
  • c-Met knockdown and selective inhibitors of c-Met, EGFR, and IGF-1R revealed independent contribution of these receptors to migration. (
  • UM can be categorized by levels of c-Met and EGFR expression which are associated with migratory/invasiveness responses to soluble factors present at high levels in the liver. (
  • We investigated the feasibility of (89)Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. (
  • HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. (
  • Epidermal growth factor receptor (EGFR) is often over-expressed or over-activated in cells of solid tumors and can be targeted by specific inhibitors (EGFRIs), like erlotinib, gefitinib, cetuximab and panitumumab. (
  • Since previous work revealed evidence for genetic, pharmacokinetic and cytokine markers, the intention of this work was to identify functional biomarkers that are able to measure EGFR inhibition variability in the periphery, especially in blood plasma and skin cells. (
  • The EGFRI cetuximab, the EGFR ligand amphiregulin (AREG) and the growth factors hepatocyte growth factor (HGF) and 25-OH-vitamin D were selected as candidates following these criteria. (
  • Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β in these cells. (
  • Transactivation of the EGFR pathway by TGF-β was impaired in Cav1(-/-) hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. (
  • Reconstitution of Cav1 in Cav1(-/-) hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. (
  • In conclusion, in hepatocytes, Cav1 is required for TGF-β-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-β pro-apoptotic effects. (
  • Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF). (
  • A novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, osimertinib, has marked efficacy in patients with EGFR-mutant lung cancer. (
  • A925L/AR cells acquired the resistance by EGFR activation resulting from AREG overexpression caused by decreased expression of microRNA-449a. (
  • EGFR TKIs and anti-EGFR antibody resensitized A925L/AR cells to alectinib in vitro. (
  • In the LMC model with A925L/AR cells, combined treatment with alectinib and EGFR TKIs, such as erlotinib and osimertinib, successfully controlled progression of LMC. (
  • In this trial, treatment efficacy and safety of retreatment with 1st generation epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI)s(Gefitinib/Erlotinib), will be assesse. (
  • The expression of several growth factors and receptors (epidermal growth factor receptor (egfr), epidermal growth factor (egf), insulin-like growth factor 1 receptor (igf1r), insulin-like growth factor 1 (igf1), insulin-like growth factor 2 (igf2), and hepatocyte growth factor (hgf)) was assessed in normal hepatocytes AML-12 cell line by RT-PCR and qPCR. (
  • found that MET promoted the development of squamous tumors by stimulating the synthesis and release of ligands that activate the epidermal growth factor receptor (EGFR). (
  • Blocking EGFR signaling caused HGF-induced squamous tumors to regress, suggesting that EGFR inhibitors might be useful for treating squamous cell carcinomas. (
  • OPN synergizes with signaling through the EGFR (epidermal growth factor) and HGF (hepatocyte growth factor). (
  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. (
  • In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte growth factor (HGF) receptor tyrosine kinase Met. (
  • We have identified a number of breast cancer cell lines that are sensitive to EGFR TKIs. (
  • Here we demonstrate that treatment of breast cancer cells sensitive to EGFR TKIs with recombinant HGF confers a resistance to EGFR TKIs. (
  • Interestingly, knocking down EGFR abrogated HGF-mediated cell survival, suggesting a crosstalk between EGFR and Met. (
  • One molecule shown to contribute to the acquired resistance to EGFR TKIs is the tyrosine kinase receptor Met. (
  • Lysophosphatidic acid induces both EGFR-dependent and EGFR-independent effects on DNA synthesis and migration in pancreatic and colorectal carcinoma cells. (
  • Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells. (
  • Targeting was further confirmed from the YI-12 peptide-EGFR competitive transfection determinations in the HepG2 cell line. (
  • These cell lines express message for the following growth factor receptors: HGFR, KGFR, EGFR, TGFβR-1, TGFβR-2, and FGFR-1(flg). (
  • Circulating FGF21 is liver derived ( 14 ), and hepatic FGF21 expression is upregulated, following extended periods of fasting, by peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor that induces the expression of numerous genes involved in mitochondrial fatty acid (FA) oxidation ( 15 ). (
  • Samadi AK, Tong X, Mukerji R, Zhang H, Timmermann BN, Cohen MS. Withaferin A, a cytotoxic steroid from Vassobia breviflora , induces apoptosis in human head and neck squamous cell carcinoma. (
  • While the extracellular domain of cadherin induces cell-cell adhesion in the presence of Ca 2+ , an interaction between the cytoplasmic domain of cadherin and the underlying actin cytoskeleton is also required for the construction of tight and compact cell-cell adhesions (for a review, see reference 32 ). (
  • Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism. (
  • In MDCK cells, hepatocyte growth factor/scatter factor (HGF/SF) induces epithelial cell dissociation, scattering, migration, growth and formation of branched tubular structures. (
  • This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. (
  • Growth/differentiation factor-5 induces angiogenesis in vivo. (
  • MMP-9 (matrix metalloproteinase 9) cleaves OPN-c, thereby releasing a 5 kDa fragment that binds to CD44 receptors and induces hepatocellular carcinoma invasion and metastasis . (
  • Independent of HIFα, hypoxia induces OPN expression in breast cancer cells, which leads to NFkB activation, VEGF expression , and angiogenesis. (
  • OPN induces the expression of oxidoreductases, which protects cells from anoikis during anchorage independent growth. (
  • In a retrospective study of 171 patients with NSCLC, OPN and thrombospondin-1 (a matrix protein that induces proliferating endothelial cells to secrete Fas ligand, which mediates apoptosis) levels were compared. (
  • The HGF/c-MET axis induces several biological responses in cancer cells, which lead to cell migration, matrix degradation, invasiveness, and induction of angiogenesis [ 15 ]. (
  • Publications] Matsumoto,K.: 'Hepatocyte growth factor/scatter scator induces tyrosine phosphrylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells. (
  • In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. (
  • Progression-associated genetic alterations are common to different tumor types and target growth-promoting and cell-cycle-controlling pathways, resulting in focal hypoxia, necrosis, and angiogenesis. (
  • These receptors with tyrosine kinase activity also exist in constitutively active mutant forms in gliomas [ 7 ], regulating several signaling pathways such as phosphoinositide-3-kinase/AKT-protein kinase B (PI3K/AKT-PKB), RAS/mitogen-activated protein kinase (MAPK), and phospholipase C/protein kinase C (PLC/PKC). (
  • SB203580 (specific inhibitor of p38) and BIX02189 (specific inhibitor of MEK5) were used to identify bFGF as the main cytoprotective factor acting via p38/MAPK and MEK5-KLF2 pathways. (
  • However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. (
  • HGF activates a variety of downstream pathways, including the mitogen-activated protein kinase (MAPK) signaling pathway which is involved in cell growth and enhances DNA synthesis of hepatocytes during liver regeneration ( 4 - 6 ). (
  • Plenty of molecular pathways define distinct types of migration and invasion in a cancer cell-autonomous manner, including single-cell amoeboid and mesenchymal migration and collective cell migration ( 1 , 2 ). (
  • In this review, we present various concepts on the signaling pathways and molecular mechanisms underlying the onset of cancer cell migration and invasion during tumor progression and metastasis. (
  • Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents. (
  • To determine which pathways are involved in Np-1-mediated facilitation of c-Met-dependent cell invasiveness, the effects of HGF on signaling were examined next in sham-transfected and Np-1-overexpressing COLO-357 cells. (
  • These findings indicate that Np-1 is required for efficient activation of c-Met-dependent pathways that promote cell invasiveness. (
  • A malignant cell phenotype is initiated when mutant cholangiocytes produce mitogens that activate local cellular receptors and intracellular signaling pathways ( 4 , 6 ). (
  • Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. (
  • Targeting Cell Survival Pathways to Enhance Response to Chemotherapy encompasses recently developed molecular targeting agents and approaches that suppress cell survival signaling. (
  • Key pathways leading to chemoresistance emanate from growth factor receptors, PI3K, STAT3, anti-apoptotic Bcl-2 family members, autophagy, and the DNA damage response pathway. (
  • Integrin receptors, which link the extracellular matrix to the cytoskeleton and various signaling pathways, are essential for cells to sense and integrate cues from the extracellular matrix. (
  • To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. (
  • Differential effects of epidermal growth factor (EGF) receptor ligands on receptor binding, downstream signalling pathways and DNA synthesis in hepatocytes. (
  • The major extracellular mediator of skeletal muscle hypertrophy is thought to be Insulin Growth Factor-1 (IGF-1) which binds to its receptor IGF1R to initiate a cascade of signaling pathways via phosphoinositide 3-kinase (PI3-K/Akt/mammalian target of rapamycin (mTOR)) [ 1 , 2 ]. (
  • Flow cytometry analysis demonstrates G2/M cell cycle arrest and apoptosis at 1 μM WA in treated cells. (
  • WA-mediated apoptosis in UM cells is partly mediated though the suppression of c-Met and Akt activation. (
  • Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells. (
  • Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5. (
  • p53 functions in a variety of ways to suppress tumor formation, including activation in the presence of DNA damage, thereby arresting the cell cycle and inducing apoptosis in damaged cells ( 17 ). (
  • Furthermore, drug screening from a library of 100 kinase inhibitors indicated that Glycogen synthase kinase-3 (GSK-3) inhibitors, such as LY2090314, markedly inhibited the growth and induced apoptosis of resistant cells, specifically those with a mesenchymal phenotype. (
  • Induction of AMPK activation by N,N'-diarylurea FND-4b decreases growth and increases apoptosis in triple negative and estrogen-receptor positive breast cancers. (
  • In vitro , ANCA IgG can activate TNF-α-primed neutrophils, causing an oxidative burst, accelerated apoptosis, and damage to vascular endothelial cells ( 1 ), suggesting that ANCA IgG plays a role in disease pathogenesis or amplification of vascular injury ( 2 ). (
  • We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. (
  • Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. (
  • Sorafenib was equally toxic to both cell lines, but only in HepG2 was activation of caspase 3/7 activity, as a sign of apoptosis, observed. (
  • especially in response to hepatocyte growth factor/scatter factor (HGF/SF). (
  • The transmembrane tyrosine kinase mesenchymal-epidermal transition (MET) receptor and its own ligand, hepatocyte growth factor, also called scatter factor, have been recently defined as novel promising targets in a number of individual malignancies, including non-small cell lung cancer (NSCLC). (
  • Publications] Komada,M.: 'Regulatory role of major tyrosine autophosphorylation site of kinase domain of c-Met receptor(scatter factor/hepatocyte growth factor receptor). (
  • Of note, increased Fgf21 expression in mice fed a high-fat diet or hepatocytes exposed to palmitate was accompanied by reduced PPARβ/δ and activation of the HRI-eIF2α-ATF4 pathway. (
  • Carpentier JL, Gazzono H, Van Obberghen E, Fehlmann M, Freychet P, Orci L: Intracellular pathway followed by the insulin receptor covalently coupled to 125 I-photoreactive insulin during internalization and recycling. (
  • Dunn WA, Connolly TP, Hubbard AL: Receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes: receptor pathway. (
  • Mutations in the retinoblastoma protein (Rb) have been identified in 20% of malignant gliomas [ 1 ] and those lacking mutations in Rb contain mutations in other molecules involved in the Rb signaling pathway, such as the cell-cycle regulator p16INK4A or cyclin-dependent kinase (CDK). (
  • Data demonstrate that targeting of Mig-7 simultaneously inhibits more than one cancer-progressing pathway while likely sparing normal cells. (
  • Furthermore, we co-cultured HGF-secreting fibroblasts with Met-expressing cancer cells to mimic the paracrine HGF/Met pathway, which is active in the tumor microenvironment. (
  • The TGFβ-SMAD3 pathway inhibits IL-1α induced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration. (
  • Serotonin (5-HT7) Receptor-Stimulated Activation of cAMP-PKA Pathway in Bovine Corneal Epithelial and Endothelial Cells. (
  • Dernovsek KD, Bar RS, Ginsberg BH, Lioubin MN: Rapid transport of biologically intact insulin through cultured endothelial cells. (
  • This study investigated the cytoprotective effects of a new laminar shear medium (LSM) derived from a modified cone-and-plate shear device and identified basic fibroblast growth factor (bFGF) secreted by human aortic endothelial cells (HAECs) as the dominant protective factor in the LSM. (
  • Evaluation of the protective effects of LSM and SM on endothelial dysfunction induced by tumor necrosis factor (TNF)-α (10 ng/mL), which leads to production of reactive oxygen species (ROS), inflammatory monocyte adhesion, and tissue factor activity. (
  • N-cadherin is expressed in neuronal and fibroblastic cells, while VE-cadherin is expressed in endothelial cells. (
  • but is now known to be widely expressed in cells of epithelial, endothelial and mesenchymal origin. (
  • In many instances, stromal cells, such as blood vessel and lymphatic endothelial cells, cancer-associated fibroblasts, or bone marrow-derived inflammatory cells, act as modulators of cancer cell migration and invasion and as pathfinders in the extracellular matrix ( 3 ). (
  • Neuropilin-1 (Np-1), a receptor for semaphorin 3A and vascular endothelial growth factor, is expressed at high levels in pancreatic ductal adenocarcinoma (PDAC). (
  • Hepatocytes, sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells in the biliary microenvironment secrete inflammatory cytokines, and it is these cytokines that may induce malignant transformation in cholangiocytes ( 4 , 5 ). (
  • In the present study, mammalian target of rapamycin (mTOR) expression in cancer cells was silenced with mTOR-siRNA (simTOR) formulated in TEPA-PCL modified with Ala-Pro-Arg-Pro-Gly (APRPG), a peptide having affinity for vascular endothelial growth factor receptor-1 (VEGFR-1). (
  • Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells. (
  • A recent study revealed thatsIGFBP7 is a novel component of endothelial cell-specific WeibelPalade bodies and binds to ultra-large von Willebrand factor stringssreleased by endothelial cells [11]. (
  • Yoshie M, Kutsukake M, Sakurai T. Insulin-like growth factor binding protein-7 (IGFBP7) blocks vascular endothelial cell growth factor (VEGF)-induced angiogenesis in human vascular endothelial cells - Tamura, Hashimoto, et al. (
  • ultra-large von Willebrand factor stringssreleased by endothelial cells [11]. (
  • Therefore, in the current study, wesdetermined the effects of LH and VEGFA on in vitro tube formationsusing luteal microvascular endothelial cells (LECs) isolated fromsthe early CL, and further exam. (
  • Relationship between prostaglandin E2 and vascular endothelial growth factor (VEGF) in angiogenesis in human vascular endothelial cells. (
  • Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1β (IL1β). (
  • Indoction in monocytes and endothelial cells by inflammatory and immunological agents with special reference to cyclosporin A 1097 Sæter Gunnar ( (
  • Publications] Morimoto,A.: 'Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascullar endothelial cells. (
  • Publications] Izumi,H.: 'Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human microvascular endothelial cells. (
  • Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and a variety of other cells, including endothelial and epithelial cells, melanocytes, and keratinocytes. (
  • Increased Fgf21 expression was observed in the livers of PPARβ/δ-null mice and in mouse primary hepatocytes when this receptor was knocked down by small interfering RNA (siRNA). (
  • siRNA analysis demonstrated that HRI regulates Fgf21 expression in primary hepatocytes. (
  • Although tyrosine phosphorylation of Eps15 has been implicated in EGF receptor internalization, the function of Eps15 ubiquitination is not known. (
  • TGFβ 1 treatment enhanced tyrosine phosphorylation of α- and β-catenin, which resulted in dissociation of the E-cadherin/catenin complex from the actin cytoskeleton and reduced cell-cell adhesion. (
  • Collectively, these data show that the TGFβ 1 -induced destabilisation of E-cadherin-mediated cell-cell adhesion involves phosphorylation of β-catenin, which is regulated by E-cadherin adhesion complex-associated PI3-kinase and PTEN. (
  • Targeting with short hairpin RNA, specific to decrease Mig-7 protein levels, inhibits carcinoma cell invasion and metastasis as well as returns ERK1/2, Akt, GSK, and S6 kinase to normal phosphorylation states through reactivation of PP2A. (
  • In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. (
  • HGF actions on c-Met tyrosine phosphorylation and p38 mitogen-activated protein kinase (MAPK) activation were increased in Np-1-overexpressing COLO-357 cells by comparison with HGF effects in sham-transfected cells. (
  • Inhibiting STAT3 expression or phosphorylation using antisense oligonucleotides and small-molecule inhibitors suppressed the growth of human and murine tumors in animal models [ 14 , 15 , 16 ], demonstrating that STAT3 is a potential target for cancer therapy. (
  • These results were coincident with attenuation of TGF-β-induced survival signals in Cav1(-/-) hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. (
  • Animal studies show that LMTK2-KD suppressed colon cancer cell xenograft growth, decreased PP1A phosphorylation and increased p-p65(Ser468). (
  • Reversible protein phosphorylation is the main strategy for con trolling activities of eukaryotic cells. (
  • Phosphorylation occurs in responseto extracellular signals (hormones, neurotransmitters, growth and differentiation factors, etc), cell cycle checkpoints, and environmental or nutritional stresses and is roughly analogous to turning on a molecular switch. (
  • We investigated the effects of inhibition of mTOR, focusing on the differences between cells treated with simTOR and those with rapamycin in terms of Akt (ser473) phosphorylation and antiproliferative effects. (
  • After nearly 50 years of investigation, the molecular target of phenobarbital induction has now been delineated to phosphorylation at threonine 38 of the constitutive androstane receptor (NR1I3), a member of the nuclear receptor superfamily. (
  • Threonine 38 is conserved as a phosphorylation motif in the majority of both mouse and human nuclear receptors, providing us with an opportunity to integrate diverse functions of nuclear receptors. (
  • Publications] Gamou,S.: 'Calphostin-c stimulates epidermal growth factor receptor phosphorylation and internalization via light-dependent mechanism. (
  • Publications] Gamous,S.: 'Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor. (
  • Bergeron JJM, Cruz J, Khan MN, Posner BI: Uptake of insulin and other ligands into receptor-rich endocytic components of target cells: the endosomal apparatus. (
  • Receptor tyrosine kinases (RTK) and their cognate ligands are key modulators of intracellular signaling and have emerged as potent regulators of molecular/cellular events involved in tumor malignancy. (
  • Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most frequent cancer worldwide. (
  • This Podcast features an interview with Stuart Yuspa, senior author of a Research Article that appears in the 21 June 2016 issue of Science Signaling , about how activation of the receptor tyrosine kinase MET stimulates the formation of squamous cell carcinoma in the skin. (
  • Aberrant MET activation has been implicated in several types of cancer, including squamous cell carcinoma. (
  • The tyrosine kinase receptor MET promotes squamous cell carcinoma by stimulating signaling through the epidermal growth factor receptor. (
  • Known major mechanisms for resistance to molecular targeted drugs include gatekeeper mutations in the target gene and activation of bypass survival signal via receptors other than the target receptors. (
  • The latter mechanism can involve receptor gene amplification and ligand-triggered receptor activation as well. (
  • Four year project to identify Hepatocyte Growth Factor (HGF) regulated gene expression and potential therapeutic implications of targeting these candidate genes. (
  • In addition, gene amplification in gliomas causes the overexpression of several mitogens and their specific receptors. (
  • The possibility to isolate GBM stem cells opens the frontier of gene replacement, knockdown, or silencing as a new therapeutic approach [ 15 ]. (
  • Further, advances in the analysis of gene expression and gene activity, coupled with a detailed knowledge of cell origins, are enhancing our understanding of kidney morphogenesis and unraveling the normal processes of postnatal repair and identifying disease-causing mechanisms. (
  • Differential gene expression in migrating renal epithelial cells after wounding. (
  • NAK-1, PAI-1, and HSP-70 were induced or stimulated only in cells at the wound edge, u-PA was stimulated in cells away from the wound, and CTGF was induced in each of these populations suggesting that cell-to-cell communication may regulate gene expression after wounding. (
  • Migration inducting gene 7 (Mig-7 or Mig7) is a gene that corresponds to a cysteine-rich protein localized to the cell membrane and cytoplasm. (
  • The new LSM and bFGF attenuated TNF-α-induced ROS induction, inflammation, and tissue factor activity and inhibited the inflammatory- and thrombosis-related gene/protein overexpression both in vitro and in vivo . (
  • The zinc-finger-containing proteins Snail, Slug and SIP1, and the helix-loop-helix transcription factor E12/E47 are important transcriptional repressors that bind to E2 boxes in the promoter of the E-cadherin gene and actively repress its expression. (
  • Aged donor cells showed a decreased potential for Hep-Dif which was rescued by ML141 treatment, giving rise to mature and functional hepatocyte-like cells as assessed by hepatic gene expression, cytochrome activity, urea and albumin production, low-density lipoprotein (LDL) uptake, and glycogen storage. (
  • The p53 DNA binding domain is the mostly commonly mutated region of the gene in DNA isolated from cancer cells ( 16 ). (
  • Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. (
  • These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. (
  • To answer these long-term puzzles and to dissect the molecular mechanism of AR in breast cells, we applied different strategies to knock out the AR gene in female mice and breast cancer MCF7 cells. (
  • Previous studies have shown that increasing the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and gene targets in cell culture and stroke animal models is highly neuroprotective. (
  • This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. (
  • This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. (
  • Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. (
  • Novel epidermal growth factor directed cationic lipoplexes promote in vitro hepatotropic gene targeting. (
  • This study serves as an evaluation of a hepatocyte-directed liposomal gene delivery system, exploiting the abundant epidermal growth factor (EGF) receptors on hepatocellular carcinoma cells (HepG2) in vitro. (
  • In vitro cytotoxicity was determined using the MTT assay, and reporter gene expression, was assayed using the luciferase and green fluorescent protein (GFP) reporter gene assays in the receptor positive HepG2 and the receptor negative Chinese Hamster ovary (CHO-K1) cell line. (
  • An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-alpha, and nonparenchymal-cell-derived TGF-beta in the regenerating liver. (
  • In the present study, we identify brigatinib to be effective against triple-mutation-harbouring cells in vitro and in vivo . (
  • Targeting with antibody generated to the peptide representing the first nine amino acids of Mig-7 detects cells expressing this protein and significantly inhibits carcinoma cell invasion in vitro. (
  • CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. (
  • In fact, bereavement of E-cadherin function is sufficient to induce tumor cell migration and invasion and tumor progression in vitro and in vivo ( 22 - 25 ). (
  • Ectopic expression of constitutive STAT3 is sufficient to induce transformation of rodent cells in vitro and tumor formation in vivo [ 3 , 13 ]. (
  • RESULTS: A925L/AR cells were moderately resistant to various ALK TKIs, such as alectinib, crizotinib, ceritinib, and lorlatinib, compared with parental cells in vitro. (
  • Mechanistic research indicated how the addition of lenalidomide during CS1 CAR T cell development in vitro improved the immune features of CS1 CAR T cells, including cytotoxicity, memory space maintenance, Th1 cytokine creation, and immune system synapse development. (
  • Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro. (
  • Migration induced by epidermal and hepatocyte growth factors in oral squamous carcinoma cells in vitro: role of MEK/ERK, p38 and PI-3 kinase/Akt. (
  • A nanosuspension composed of titanium dioxide as inorganic sunscreen within a matrix of carnauba wax and decyl oleate in a 2:1 ratio has previously been reported to yield high sun protection factors (SPF) in vitro. (
  • In vitro sun protection factors representing an indicator of the UVA/UVB protective property of the sunscreen formulation were determined with an SPF analyzer and calculated from the monochromatic protection factor, the solar irradiance and the erythemal constants. (
  • HGF-induced DNA synthesis in hepatocytes is suppressed by p38. (
  • The extracellular domains of cadherins form Ca 2+ -dependent homophilic adhesions between neighboring cells. (
  • These findings suggest that HB-EGF can not only modulate HGF/SF-induced cellular responses in MDCK cells but also that membrane-bound HB-EGF and soluble HB-EGF give rise to distinctly different effects on cell-cell and cell-extracellular matrix interactions. (
  • SB203580, an inhibitor of p38 MAPK, suppressed HGF-induced invasion in Np-1-overexpressing cells, whereas U0126, a MAP/extracellular signal-regulated kinase kinase inhibitor, was without effect. (
  • The tumor microenvironment (TME), which includes various types of cells and extracellular components, mediates tumor progression and affects treatment efficacy. (
  • Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes. (
  • Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. (
  • HGF is synthesized by non-parenchymal (particularly stellate) cells in the liver and binds to the c-Met receptor of hepatocytes. (
  • EGF administered in vivo binds to cells in the enamel organ of developing teeth (Martineau-Doize,et al. (
  • Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics. (
  • We have used biochemical and morphological techniques to demonstrate that hepatocytes in the perfused liver bind, internalize, and degrade substantial amounts of murine epidermal growth factor (EGF) via a receptor-mediated process. (
  • When saturating concentrations of EGF were perfused through a liver at 35 degrees C, ligand clearance was biphasic with a rapid primary phase of 20,000 molecules/min per cell that dramatically changed at 15-20 min to a slower secondary phase of 2,500 molecules/min per cell. (
  • Fibroblast growth factor 21 (FGF21), a member of the FGF family, is a hormone with a wide range of endocrine and autocrine actions on carbohydrate and lipid metabolism ( 1 ) and is considered a novel therapeutic target for the treatment of nonalcoholic fatty liver disease (NAFLD), insulin resistance, and type 2 diabetes. (
  • The pleiotropic effects of FGF21 on target tissues, including adipose tissue, β-cells, and liver ( 1 , 2 , 10 ), are mediated by its binding to FGF receptors in a β-klotho-dependent manner ( 11 - 13 ). (
  • In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitis C (CHC) virus, liver cirrhosis (LC) and HCC. (
  • Major risk factors for HCC include infection with hepatitis B (HBV) and C (HCV) viruses, alcoholic liver disease, and possibly non-alcoholic fatty liver disease. (
  • Growth factors, such as hepatocyte growth factor (HGF), epidermal growth factor (EGF) or insulin growth factor (IGF) and cytokines, such as IL-6 or TNF-α, have been shown to play important roles in the early phase of liver regeneration by using rodent PH models ( 4 - 6 ). (
  • TNF-α, as an initiation factor of liver regeneration, stimulates Kupffer cells in the liver. (
  • However, studies on TNF-α and IL-6 knockout mice have demonstrated that these factors are not key to liver regeneration ( 7 , 8 ). (
  • Togo et al reported 23 genes, including Karyopherin α1 and interleukin-1 receptor associated kinase-1 ( IRAK-1 ), as novel genes involved in the early phase of liver regeneration by microarray analysis ( 9 ). (
  • We further explored the relationship between c-Met and other growth factor receptors prevalent in the liver and their roles in UM metastatic potential. (
  • Orotic acid, nucleotide-pool imbalance, and liver-tumor promotion: a possible mechanism for the mitoinhibitory effects of orotic acid in isolated rat hepatocytes. (
  • Several important clinical risk factors exist for cholangiocarcinoma such as female gender, Caroli's disease, congenital choledochal cysts, primary sclerosing cholangitis, hepatolithiasis, ampulla of Vater adenomas, Opistorchis viverrini and Clonorchis sinensis liver fluke infestation, Salmonella typhi infection, and obesity. (
  • On histology, INF-alpha at 6750 IU/kg failed to prevent fibrosis in liver of BDL rats, although many of the hepatocytes appeared normal, while the higher dose of resulted in some improvement in the degree of fibrosis, oedema and lymphocytic infiltration. (
  • Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-β in liver cancer cells. (
  • Human adipose-derived mesenchymal stem cells (hADSCs) are promising cells that may promote hepatocyte differentiation (Hep-Dif) and improve liver function, but the involvement of Cdc42, a key small RhoGTPase which plays a crucial role in aging, is still not well established. (
  • While the differentiation potential of MSCs is comparatively limited to that of embryonic stem cells or induced pluripotent stem cells, they are a much safer source regarding the risk of inducing teratoma and raise less ethical debates when it comes to clinical applications, particularly in liver diseases [ 6 ]. (
  • However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. (
  • Given the caveat that PB induction is a liver-predominant event, various hepatocyte-enriched nuclear receptors were screened. (
  • sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. (
  • Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. (
  • Vertebrate hepatocyte growth factor-regulated tyrosine kinase substrate (HRS). (
  • Increased Fgf21 was associated with enhanced protein levels in the heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI). (
  • We show that a neutralizing anti-HGF monoclonal antibody (L2G7) potently inhibits tumor growth and the activation of Akt and mitogen-activated protein kinase (MAPK) in PTEN-null/HGF + /c-Met + /EGFRvIII − U87 glioma xenografts (U87wt). (
  • Here we show that the epithelial dedifferentiation, accompanied by dissociation of the E-cadherin adhesion complex, induced by TGFβ 1 depended on phosphatidylinositol 3-kinase (PI3-kinase) and the phosphatase PTEN as analysed in PANC-1 and Smad4-deficient BxPC-3 pancreatic carcinoma cells. (
  • Collectively our results demonstrate that UBPy is essential for receptor tyrosine kinase stability and to maintain proper endosomal transport in vivo. (
  • In this paper, we report a novel functional role of casein kinase 1 (CK1) in the regulation of cell-cell contacts. (
  • The Met tyrosine kinase receptor and its ligand hepatocyte growth factor are expressed in hepatocytes. (
  • PP2, a Src inhibitor, and LY294002, a phosphatidylinositol 3-kinase inhibitor, also suppressed HGF-induced invasion in these cells. (
  • Resistance mechanisms were analyzed using several assays, including Western blot and receptor tyrosine kinase array. (
  • Efficacy and Safety of ALK Tyrosine Kinase Inhibitors in Elderly Patients with Advanced ALK-Positive Non-Small Cell Lung Cancer: Findings from the Real-Life Cohort. (
  • Upon activation of the B cell antigen receptor (BCR), the spleen tyrosine kinase (Syk) and the Src family kinase Lyn phosphorylate tyrosines of the immunoreceptor tyrosine-based activation motif (ITAM. (
  • Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer. (
  • The defective development of AR −/− mammary glands involves the defects of insulin-like growth factor I-insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. (
  • To detect FMS-like tyrosine kinase-3 internal tandem duplicate (FLT3 ITD) mutation, Myeloproliferative leukemia virus oncogene (cMPL) and Ephrin A 4 receptor (EphA4) expressions in Acute myeloid leukemia (AML) and their correlation to patient's clinicopathological characteristics and survival. (
  • 2019. Incorporating MicroRNA into molecular phenotypes of circulating tumor cells enhances the prognostic accuracy for patients with metastatic breast cancer . (
  • Adenosine diphosphate, a potent stimulator of cell migration which enhances expression of u-PA and PAI-1 in nonwounded cultures, additively stimulates these genes after wounding and may thereby potentiate wound healing. (
  • The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. (
  • Currently, one targeted therapy, trastuzumab, is approved for the treatment of advanced human epidermal growth factor receptor (HER)-positive gastric cancer, but others are in late-stage clinical development [5]. (
  • Clonal growth of normal human epidermal keratinocytes in a defined medium. (
  • Generally, male breast cancer has more favorable tumor characteristics than female breast cancer, such as lower tumor grade, a higher incidence of estrogen receptor (ER) expression, and a lower incidence of human epidermal growth factor receptor 2 (HER2) expression [ 1 , 3 ]. (
  • PURPOSE: c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. (
  • Fibroblast growth factor 21 (FGF21), a peptide hormone with pleiotropic effects on carbohydrate and lipid metabolism, is considered a target for the treatment of diabetes. (
  • The number of IL-1 receptors (IL-1R) on the fibroblast surface was analyzed by flow cytometry. (
  • Therefore, next generation sequencing (NGS) was performed in keratinocyte and fibroblast cultures from healthy donors to compare miRNA profiles between cells previously identified as rather erlotinib-sensitive and those identified as rather erlotinib-insensitive. (
  • TGF-β3, or fibroblast growth factor 1 (FGF-1). (
  • To determine whether the proteases required to activate pro-HGF were present in the breast cancer cells, we utilized a fibroblast cell line expressing pro-HGF (RMF-HGF). (
  • FGF-7), epidermal growth factor (EGF), transforming growth factor β1 (TGFβ1), and basic fibroblast growth factor (FGP-2) in both cell lines. (
  • Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. (
  • HGF has powerful mitogenic, motogenic, and morphogenic activities in various cell types, 5 - 8 and its receptor c-Met is highly expressed on corneal epithelial cells. (
  • p38 differentially regulates ERK, p21, and mitogenic signalling in two pancreatic carcinoma cell lines. (
  • Functional heterogeneity in tumor-derived human pancreatic stellate cells: Differential expression of HGF and implications for mitogenic signaling and migration in pancreatic cancer cells. (
  • The involvement of the docking protein Gab1 in mitogenic signalling induced by EGF and HGF in rat hepatocytes. (
  • Epidermal growth factor binding and mitogenic activity on purified populations of cells from the. (
  • Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. (
  • To investigate how mitomycin C (MMC) modulates hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) secretions in human corneal fibroblasts and regulates human corneal epithelial (HCE) cell migration. (
  • 1 After wounding from photorefractive keratectomy (PRK) or laser in situ keratomileusis, the injured epithelial cells release substantial amounts of IL-1 as a master regulator, 1 , 2 and they upregulate hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in fibroblasts. (
  • Anderson RGW, Brown MS, Goldstein JL: Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. (
  • The effect of MMC-treated fibroblasts on HCE cell migration was evaluated using a transwell migration assay. (
  • Conditioned medium from MMC-treated fibroblasts exerted a similar concentration-dependent effect on HCE cell migration, enhancing migration most significantly at 0.05 mg/mL MMC in the presence of IL-1β. (
  • The MMC dose-dependent modulation of HCE cell migration was abolished in HGF-silenced fibroblasts. (
  • In the presence of IL-1β, MMC-treated corneal fibroblasts modified HCE cell migration through IL-1β-induced HGF secretion. (
  • Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). (
  • Consequently embryonic fibroblasts undergo growth arrest upon induced deletion of UBPy. (
  • PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into SCID mice and the therapeutic effects of E7050 plus gefitinib were assayed. (
  • In fact, HGF, the ligand for Met, is not expressed in epithelial cells but is secreted by fibroblasts in the tumor stroma. (
  • Publications] Hattori,A.: 'Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gammma in stimulating the prodution of nerve growth factor in fibroblasts. (
  • Publications] Hukami,J.: 'Transforming growth factor-beta has both promoting and inhibiting effects on induction of DNA synthesis in human fibroblasts. (
  • With lZ5I-EGFradioautography, a high number of binding sites for EGF were detected on the cell membranes of basal cells of oral epithelium, papillary cells of the enamel organ, periodontal ligament fibroblasts, and @ 1988 ALAN R. LISS, INC preosteoblasts. (
  • The former gives rise to the cells of the collecting duct system, whereas the latter gives rise both to the epithelial components of the nephrons (excluding collecting duct) as well as stromal and vascular elements. (
  • 7 This vascular deficiency correlated with the presence of the dense stromal matrix that makes up the bulk mass of PDA tumours, and chemical inhibition of stromal cells decreased the matrix and increased intratumoral perfusion and therapeutic delivery. (
  • Hepatocytes were grown in chemically defined hepatocyte growth medium (HGM) containing hepatocyte growth factor (HGF) and epidermal growth factor (EGF) on collagen-coated polystyrene beads in roller bottle cultures, forming clusters of beads, and proliferating hepatocytes and nonparenchymal cells, including fenestrated endothelium-forming vascular structures. (
  • Mammalian epidermal growth factor receptor substrate 15 (EPS15), which is involved in cell growth regulation. (
  • We investigated the role of peroxisome proliferator-activated receptor (PPAR) β/δ deficiency in hepatic FGF21 regulation. (
  • absence of regulation by receptor occupancy. (
  • Donner DB: Regulation of insulin binding to isolated hepatocytes: correction for bound hormone fragments linearizes Scatchard plots. (
  • Np-1 overexpression was associated with enhanced cell invasiveness in response to hepatocyte growth factor (HGF), and this effect was abolished by small interfering RNA-mediated down-regulation of c-Met. (
  • In this review, we outlined TME factors and molecular events involved in the regulation of non-cell-autonomous resistance of cancer, summarized how the TME contributes to non-cell-autonomous drug resistance in different types of antineoplastic treatment, and discussed the novel strategies to investigate and overcome the non-cell-autonomous mechanism of cancer non-cell-autonomous resistance. (
  • Profile of MMP and TIMP expression in human pancreatic stellate cells: regulation by IL-1? (
  • Regulation of erythropoiesis in the neonatal mammal during the growth period. (
  • Regulation of the LDL receptor in parenchymal and non-parenchymal cell 1087 Olsvik Ørjan (dr.philos. (
  • Hormone regulation of Sertoli cell adenylate cyclase, - mechanisms of antagonistinduced desensitization 1095 Kaasa Stein ( (
  • The underlying mechanism of CAR regulation is dephosphorylation of threonine 38, which can be inhibited by epidermal growth factor (EGF) to inactivate CAR ( Fig. 1A ) or induced by PB to activate CAR ( Fig. 1B ). (
  • The transcriptional regulation of TEAD1 to muscle-specific genes is implemented by co-operation with numerous co-factors, including MEF2 [ 8 ]. (
  • The four Notch genes identified in mammals ( Notch 1-4 ) are expressed in a wide variety of cells and play a significant role in cellular differentiation. (
  • The activation of Notch by cell-to-cell interaction causes a transcriptional silencing effect that inhibits differentiation in some cells but not in others ( 16 - 18 ). (
  • ML141 has the potential to reverse the age-related aberrations in aged stem cells and promotes their hepatogenic differentiation. (
  • Cholesterol sulfate accumulation in tumorigenic and nontumorigenic rat esophageal epithelial cells: evidence for defective differentiation control in tumorigenic cells. (
  • Bone morphogenetic proteins and growth and differentiation factors in the human cornea. (
  • growth- differentiation factor (GDF)-5), and BMP receptors (BMPR) types I (BMPR-IA, BMPR-IB) and II (BMPR-II) was investigated by reverse transcription-polymerase chain reaction (RT-PCR) in ex vivo and cultured cells. (
  • Growth/differentiation factor 5 protects nigrostriatal dopaminergic neurones in a rat model of Parkinson's disease. (
  • Finally, in vivo Sema3A was upregulated in the differentiation phase of satellite cells isolated from muscle regenerating following crush injury. (
  • These recent demonstrations of the binding of EGF to various odontogenic tissues suggests that this growth factor may have a significant role in the differentiation of the enamel organ and dental follicle mesenchyme. (
  • Myostatin (MSTN) is a member of the transforming growth factor-b (TGF-b) superfamily of secreted growth and differentiation factors [ 9 ]. (
  • ProHB-EGF is proteolytically cleaved to release a soluble ligand (sHB-EGF) that activates the EGF receptor. (
  • This review focuses specifically on receptor activation by ligand stimulation and discusses novel therapeutic strategies that are under development for overcoming resistance to molecular targeted drugs in lung cancer. (
  • The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of JNJ-61186372 as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D)(monotherapy) and recommended Phase 2 combination dose (RP2CD) (combination therapy) in participants with advanced non-small cell lung cancer (NSCLC). (
  • This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC). (
  • Elevated integrin α6β4 expression is associated with venous invasion and decreased overall survival in non-small cell lung cancer. (
  • S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide. (
  • Preclinical experiments with osimertinib-resistant lung cancer cells showed that EMT was associated with decreased microRNA-200c and increased ZEB1 expression. (
  • BACKGROUND: A BRAF V600E mutation is found as driver oncogene in patients with non-small cell lung cancer. (
  • In 27 patients with NSCLC (non-small cell lung cancer), OPN levels at the completion of radiation, as well as the change in plasma concentration during therapy, was predictive of overall survival. (
  • Quality of life and survival in patients with non small cell lung cancer 1096 Carlsen Erik ( (
  • This increase caused enhanced levels of phosphorylated eIF2α and activating transcription factor (ATF) 4, which is essential for Fgf21 -induced expression. (
  • The influence of MMC on HGF expression/secretion and HCE cell migration was further confirmed by RNA interference. (
  • Constitutive expression is repressed at 1 hour for transcripts that encode receptors for fibronectin (FN), epidermal growth factor, and hepatocyte growth factor (c-met), and the secreted proteins FN and osteopontin. (
  • Expression of genes encoding transforming growth factor (TGF)-beta 1 and -beta 2, retinoic acid receptor alpha, int-1, int-2, and gap junction protein which can play a role in cell movement, appeared unchanged after wounding. (
  • Induction of Mig-7 expression occurs downstream of Epidermal growth factor/Epidermal growth factor receptor, Cox-2/PGE-2 or Hepatocyte growth factor/c-Met activation and signalling. (
  • Data has shown that Mig-7 expression is specific to human embryonic/fetal cytotrophoblast cells and epithelial type cancer cells, while not expressed in normal cells. (
  • Mig-7 expression is found on, as well as in, epithelial tumor cells at the primary site, secondary (metastatic) sites, and blood from cancer patients. (
  • Although NHE5 expression is undetectable in normal astrocytes, C6 glioma cells express NHE5 at an elevated level. (
  • Expression of noncleavable membrane-anchored HB-EGF promoted cell-matrix and cell-cell interactions and decreased cell migration, HGF/SF-induced cell scattering and formation of tubular structures. (
  • By contrast, expression of soluble HB-EGF induced increased cell migration, decreased cell-matrix and cell-cell interactions and promoted the development of long unbranched tubular structures in response to HGF/SF. (
  • Concomitant with its loss, expression of the mesenchymal cell-cell adhesion molecule N-cadherin is increased, a process also known as the cadherin switch ( 20 , 21 ). (
  • In addition, hypoxic conditions, frequently existing in a tumor microenvironment, induce cancer cell expression of c-Met, the bona fide receptor of HGF, and CXCR4, the signaling receptor of the chemokine CXCL12 (SDF1), and further stimulate cancer cell migration and dissemination ( 35 , 36 ). (
  • Loss of cadherin-E expression can favor the malignant phenotype by allowing easy disaggregation of cells, which can then invade locally or metastasize. (
  • Reduced cell-surface expression of E-cadherin has been noted in many types of cancers, including those that arise in the esophagus, colon, breast, ovary, and prostate . (
  • Interestingly, MTA3, a recently identified component of the Mi-2/NuRD transcriptional co-represssor complex, links Snail expression to oestrogen-receptor (ER) activity: ER signalling upregulates MTA3 to repress Snail expression. (
  • Metastatic cancer cells showed complete loss of p53 expression when compared with primary tumors. (
  • In conclusion, our observation indicates that DNOP, through an increase in the expression of egf, acts as a proliferative agent in normal mouse hepatocytes. (
  • Following implantation of the cell clusters in Matrigel, there was decreased expression of c-met, urokinase, urokinase receptor, and TGF-β1. (
  • Here we show that expression of a neural secreted chemorepellent semaphorin 3A (Sema3A) is remarkably upregulated in satellite cells of resident myogenic stem cells that are positioned beneath the basal lamina of mature muscle fibers, when treated with hepatocyte growth factor (HGF), established as an essential cue in muscle fiber growth and regeneration. (
  • Neutralizing antibody to the HGF-specific receptor, c-met, did not abolish the HGF response, indicating that c-met may not mediate the Sema3A expression signaling. (
  • Overall, the data highlight a heretofore unexplored and active role for satellite cells as a key source of Sema3A expression triggered by HGF, hence suggesting that regenerative activity toward motor innervation may importantly reside in satellite cells and could be a crucial contributor during postnatal myogenesis. (
  • Publications] Tannapfel,A.: 'Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines. (
  • Publications] Nakayama,Y.: 'Enhanced invasive activity and decreased expression of tissue inhibitors of metalloproteinases by hepatocyte growth factor in human renal cancer cells. (
  • Sir Francis Crick said: "DNA is, in fact, so precious and so fragile that we now know that the cell has evolved a whole variety of repair mechanisms to protect its DNA from assaults by radiation, chemicals and other hazards. (
  • My current research focuses on the mechanisms involved in prostate and breast cancer cell homing to the bone environment. (
  • Research project exploring potential mechanisms responsible for the metastatic dissemination and predisposition of prostate cancer cells to the bone environment. (
  • One of these relates to the issue of whether the enhanced G protein activation is restricted to immortalized B lymphoblasts, ie, cells that are not likely to play a major role in the pathogenetic mechanisms leading to EH, or whether this abnormality is expressed in nontransformed cells as well. (
  • However, the molecular mechanisms that regulate cell-cell contacts are not fully understood. (
  • Current molecular mechanisms of cholangiocarcinogenesis focus on growth regulatory genes and chronic biliary inflammation. (
  • Although specialized niches usually protect stem cells from age-dependent stress mechanisms, these cells can seemingly grow old [ 4 ]. (
  • Cell survival signaling attenuates the effectiveness of conventional chemotherapy and numerous mechanisms have been described, and continue to be described, which contribute to cell survival in the face of chemotherapy treatment. (
  • New advances have underscored the potential of targeting each of these cell survival mechanisms to improve responsiveness to chemotherapy. (
  • A new concept is therefore proposed in which tumor cell resistance to targeted therapy may be due to non-cell-autonomous mechanisms. (
  • However, knowledge of non-cell-autonomous mechanisms of resistance to different treatments is not comprehensive. (
  • Although most of these mechanisms have been validated in patients, models of tumor cell-derived resistance have apparent limitations. (
  • Thus, a new concept has been proposed in which tumor cells resistance to antineoplastic agents may be due to both cell-autonomous and non-cell-autonomous mechanisms. (
  • Mechanisms involved in PGE2-induced transactivation of the epidermal growth factor receptor in MH1C1 hepatocarcinoma cells. (
  • Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits Gα i2 , Gα i3 , Gβ 1 , and Gβ 2 from NT and HT cell lines yielded no evidence for mutations in these genes. (
  • Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. (
  • An important negative control mechanism in the signaling of epidermal growth factor (EGF) is the endocytosis and subsequent degradation of activated EGF receptors. (
  • My research focuses on Hepatocyte Growth Factor (HGF) signaling and the importance of the cytoskeletal associated protein Epithelial Protein Lost In Neoplasm (EPLIN) in cancer metastasis and assocaited therapeutic potentials. (
  • Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. (
  • We therefore considered Met/hepatocyte growth factor signaling as a candidate migration/growth factor for UM cells. (
  • Cholangiocytes secrete cytokines such as IL(Interleukin)6, transforming growth factor-beta (TGF-beta), IL8, tumor necrosis factor-alpha (TNF-alpha), and platelet-derived growth factor (PDGF) beta chain, all of which regulate biliary cell homeostasis through paracrine signaling ( 10 , 11 ). (
  • During carcinogenesis, aberrant cytokine stimuli alter cholangiocyte intracellular signaling, which contributes to the development and growth of biliary tract carcinomas ( 6 , 12 ). (
  • Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-β receptors trafficking and signaling. (
  • My lab is interested in understanding how integrins and integrin-mediated signaling contribute to the late stages of carcinoma progression where cells acquire the ability to invade into the surrounding tissues. (
  • Signaling from integrin receptors is critical for carcinoma cell invasion. (
  • Similar growth retardation and defects in growth factor-mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR −/− MCF7 breast cancer cells. (
  • It is contentious whether these signaling events are initiated by ANCA F(ab′) 2 binding to MPO or PR3 ( 2 , 5 ) or proceed via antibody binding to FcγRIIa and FcγRIIIb receptors ( 6 - 8 ) or both. (
  • Integration of BMP/Wnt signaling to control clonal growth of limbal epithelial progenitor cells by niche cells. (
  • Presently available data suggest that ≈30% to 50% of patients with EH display an enhanced Na + -H + exchange activity in blood cells and that this phenotype coincides with an increased body mass index, left ventricular hypertrophy, insulin resistance, renal Na + retention, low plasma renin, and, in the presence of type-1 diabetes, an increased susceptibility of developing nephropathy. (
  • Monolayer cultures of high-density, quiescent renal epithelial cells of the BSC-1 line were subjected to scrape wounding and then Northern blot analysis was employed to identify genes that mediate cell migration. (
  • Thus scrape wounding of renal epithelial cells is followed by induction, stimulation, or repression of specific genes with distinct responses in different populations of cells. (
  • More particularly, it concerns the treatment of renal injury by the administration of a mixture of bone-derived growth factors. (
  • Publications] Kawaida,K.: 'Hepatocyte growth factor prevents acute renal failure and accelerate renal regeneration in mice. (
  • Phenotype analysis of female mice lacking androgen receptor (AR) deficient ( AR −/− ) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. (
  • Cell specific targeting may be attained through cationic vector manipulation to favourably utilise overexpressed cancer cell specific receptors. (
  • Eps15 and its related partner Eps15R play a key role in clathrin-mediated endocytosis of transmembrane receptors. (
  • Mammalian epidermal growth factor receptor substrate EPS15R. (
  • It is estimated that more than 1000 of the 10,000 proteins active in a typical mammalian cell are phosphorylated. (
  • Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells. (
  • Despite major efforts in metastasis research, we still lack detailed insights into how cancer cells actually migrate out of primary tumors and invade into neighboring tissue, how they enter (intravasate) into the blood or the lymphatic circulation, how they survive "homelessness" and immune surveillance in the bloodstream, and how they target certain organs to leave (extravasate) the blood circulation and to initiate metastatic outgrowth in specific target organs. (
  • Similar to developmental processes like gastrulation or neural crest cell migration, differentiated epithelial tumor cells lose their epithelial morphology and migrate to a distant site to form a new structure, in this case secondary tumors. (
  • Constitutive activation of STAT3 has been reported in many human cancer cell lines and primary tumors, and this activation is associated with poor outcomes of a number of cancers. (
  • AR is expressed in normal breast cells, and up to 85% of breast tumors are AR positive ( 8 - 10 ). (
  • Also, 25-82% of metastatic breast tumors, which are estrogen receptor (ER) and progesterone (P) receptor (PR) negative, still express a significant amount of AR ( 9 , 11 ). (
  • Cancer cells typically interact with stromal cells within solid tumors in vivo, and these interactions extensively contribute to tumor development and therapeutic resistance. (
  • Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15% of the cases presenting disease persistence or recurrence after initial treatment. (
  • E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. (
  • Small peptides within the range of the OPN-5 kDa fragment that induced hepatocellular carcinoma cells blocked the CD44-mediated invasion of these cells. (
  • Recent years have seen a considerable emphasis on growth factors and the elucidation of their mode of function, which has led to the recognition that growth factors, their receptors as well as downstream elements of signalling associated with their function might be potential targets in therapeutic management of human diseases. (
  • Thymidine incorporation in hepatocytes in the presence of EGF and IGF-II was inhibited by soluble receptor (50% inhibition at 212 +/- 45 ng/ml). (
  • Although soluble receptor blocked IGF-II binding to hepatocytes, inhibition of EGF-stimulated DNA synthesis was not due to inhibition of EGF binding or uptake by the cell. (
  • Inhibition of Cdc42 by ML141 was realized during two phases: initiation (days -2 to 14 (D-2/14)) from undifferentiated to hepatoblast-like cells, or maturation (days 14 to 28 (D14/28)) from undifferentiated to hepatocyte-like cells. (
  • All of these results suggest that EGF receptors are internalized and that their rate of recycling to the surface from intracellular sites is governed by the rate of entry of ligand and/or receptor into lysosomes. (
  • Ackerman GA, Wolken KW: Histochemical evidence for the differential surface labeling, uptake and intracellular transport of a colloidal gold-labeled insulin complex by normal human blood cells. (
  • Recent studies revealed distinct differences in intracellular signal transduction between these NT and HT cell lines. (
  • In this work, we show that immortalized Cav1(-/-) hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-β, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). (
  • Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells. (
  • 2019. Importance of activated leukocyte cell adhesion molecule (ALCAM) in prostate cancer progression and metastatic dissemination . (
  • Several lines of evidence suggest that phosphatases represent important regulators of E-cadherin-mediated cell-cell adhesion. (
  • We found that NHE5 depletion greatly abrogated endocytic recycling and the protein stability of β1-integrin, which in part accounted for the defective cell adhesion, spreading, and invasion of NHE5 -knockdown cells. (
  • The molecular details of actin cytoskeleton remodeling and changes in cell-substrate adhesion during cell migration and invasion have been recently summarized in several excellent reviews ( 5 - 11 ). (
  • One of the hallmarks of EMT and the concomitant induction of cell migration and invasion is the loss of the epithelial cell-cell adhesion molecule E-cadherin, the major component of epithelial adherens junctions. (
  • Address correspondence to Joanne E. Murphy-Ullrich, Dept. of Pathology and The Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, VH 668 1530, 3rd Ave. South, Birmingham, AL 35294-0019. (
  • Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). (
  • Cadherin-1 (cadherin-E) is a specific calcium ion-dependent cell adhesion molecule. (
  • E-cadherin is simultaneously a major cell-adhesion molecule, a tumour suppressor protein, a determinant of cell polarity and a partner to the potent catenin signalling molecules. (
  • E-cadherin-mediated cell-cell adhesion is lost during the development of most epithelial cancers. (
  • In most cancers of epithelial origin, E-cadherin-mediated cell-cell adhesion is lost concomitantly with progression towards tumour malignancy. (
  • IGFBP7 is also known assIGFBP-related protein (IGFBP-rP) 1, mac25, angiomodulin (AGM),stumor-derived adhesion factor (TAF), and prostacyclin-stimulatingsfactor (PSF). (
  • The mechanism for ulcer repair represents a different entity of process including the balance of cell damage and repair at the ulcer site. (
  • This study was designed to determine the possible mechanism by which orotic acid exerts its mitoinhibitory effect on rat hepatocytes in primary culture. (
  • Previous results have indicated that in hepatocytes, Cav1 is required for TGF-β-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. (
  • Noninherent-adaptive drug resistance refers to a non-cell-autonomous mechanism in which the resistance lies in the treatment process rather than genetic or epigenetic changes, and this mechanism is closely related to the TME. (
  • To begin, the current cell signal/molecular mechanism of phenobarbital (PB) induction/constitutive androstane receptor (CAR) activation is depicted in Fig. 1 . (
  • On the molecular level, binding of TGFβ to type II TGFβ receptors leads to recruitment and transphosphorylation of type I TGFβ receptors and activation of receptor-activated Smad2 and Smad3, which then hetero-oligomerise with the common partner Smad4. (
  • A better understanding of cholangiocarcinoma tumor initiation, promotion, and progression, as well as neurotransmitter, neuroendocrine, and endocrine growth effects, may elucidate molecular targets for diagnostic and therapeutic purposes. (
  • both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) show great potential. (
  • Cadherin-based cell-cell contacts are not static but are often dynamically modulated during various physiological and pathological processes including mitosis, oncogenesis, and epithelial-mesenchymal transition during embryonic development. (
  • Current research is focusing on changing any feature that could possibly slow down the progression of aging, and mesenchymal stem cells (MSCs) [ 5 ] have emerged as a promising tool and an attractive stem cell source for this purpose. (
  • Hepatocyte growth factor (HGF) is produced by mesenchymal cells and stimulates MET, which is present on the surface of epithelial cells. (
  • This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. (
  • Insulin-like growth factor-II/mannose 6-P (IGF- II/M6P) receptor is released from cultured cells and tissues in a soluble form that retains its affinity for IGF-II. (
  • To test the possibility that soluble receptor can therefore modulate the activity of IGF-II, we determined the effect of purified soluble receptor on DNA synthesis in cultured rat hepatocytes stimulated with epidermal growth factor (EGF) (5 ng/ml) and IGF-II (200 ng/ml). (
  • These results suggest that soluble IGF-II/M6P receptor not only plays a role in modulating the action of IGF-II but may also have IGF-independent actions on cells, possibly by modulating M6P protein action. (
  • We also found that concentrations of soluble c-KIT and hepatocyte growth factor tended to predict response to sorafenib. (
  • Using MDCK cells stably expressing proHB-EGF, a noncleavable deletion mutant of proHB-EGF or soluble HB-EGF, we show that epithelial cell functions differ depending on the form of HB-EGF being expressed. (
  • This inhibitory effect was removed by immunodepletion of receptor from the purified preparation, demonstrating the absence of nonspecific cytotoxic effects of the preparation. (
  • HBGF-1 reduced the inhibitory effect of transforming growth factor type beta (TGF-beta) on the EGF stimulus. (
  • reference 1 ), a transcriptional factor that belongs to the nuclear receptor superfamily ( 2 ), in female organs remains unclear. (
  • PURPOSE To investigate transcription of members of the transforming growth factor (TGF)-beta superfamily and corresponding receptors in human corneal epithelium and stroma. (
  • Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts), are making their way into glioma treatment as another type of cell-based therapy using the antibody to bind to the specific target(s). (
  • Synthetic biology of B cell activation: understanding signal amplification at the B cell antigen receptor using a rebuilding approach. (
  • The maintenance of the structural and functional integrity of epithelia requires highly dynamic cell-cell and cell-matrix interactions. (
  • Commonly Used Pancreatic Stellate Cell Cultures Differ Phenotypically and in Their Interactions With Pancreatic Cancer Cells. (
  • However, other papers also suggested that androgens could negatively regulate the growth of mammary epithelial and breast cancer cells ( 5 - 7 ). (
  • Before ligand exposure, about 300,000 high-affinity receptors were detectable per cell, displayed no latency, and co-distributed with conventional plasma membrane markers. (
  • HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-alpha stimulus. (
  • Davies PJA, Davies DR, Levitzki A, Maxfield FR, Milhaud P, Willingham MC, Pastan IH: Transglutaminase is essential in receptor mediated endocytosis of alpha-2-macroglobulin and polypeptide hormones. (
  • However, cancer cells can also migrate and invade in the absence of EMT and may use a broad repertoire of cell migration and invasion ( 18 , 19 ). (
  • PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. (
  • In the sorafenib cohort, trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline ( P of interaction = 0.081 and 0.073, respectively). (
  • We aimed to investigate these factors in male breast cancer and correlate them with patient survival. (