Epidermal Growth Factor: 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.Receptor, Epidermal Growth Factor: 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.Transforming Growth Factor alpha: 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.QuinazolinesTransforming Growth Factors: 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.Signal Transduction: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Vascular Endothelial Growth Factor A: 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.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Fibroblast Growth Factor 2: 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).Receptor, erbB-2: 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.Platelet-Derived Growth Factor: 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.Transforming Growth Factor beta: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cells, Cultured: 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.Fibroblast Growth Factors: 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.Insulin-Like Growth Factor I: 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.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.Cell Line, Tumor: A cell line derived from cultured tumor cells.Hepatocyte Growth Factor: 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.Intercellular Signaling Peptides and Proteins: 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.RNA, Messenger: 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.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Endothelial Growth Factors: 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.Tumor Cells, Cultured: 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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Enzyme Activation: 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.Vascular Endothelial Growth Factors: 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.Antibodies, Monoclonal, Humanized: 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.Breast Neoplasms: Tumors or cancer of the human BREAST.Molecular Sequence Data: 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.Lung Neoplasms: Tumors or cancer of the LUNG.Genes, erbB-1: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Nerve Growth Factor: 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.Transfection: 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.Receptors, Platelet-Derived Growth Factor: 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.Blotting, Western: 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.Mutation: 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.Receptors, Cell Surface: 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.Proto-Oncogene Proteins: 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.Receptors, Fibroblast Growth Factor: 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.Mitogen-Activated Protein Kinases: 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).Receptor, erbB-3: 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.Mice, Nude: 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.Amino Acid Sequence: 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.Carcinoma, Squamous Cell: 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)Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Transforming Growth Factor beta1: 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.Kinetics: The rate dynamics in chemical or physical systems.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Fibroblast Growth Factor 1: 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).Phosphatidylinositol 3-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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Insulin-Like Growth Factor II: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Proto-Oncogene Proteins c-akt: 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.3T3 Cells: 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.Protein Binding: 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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.MAP Kinase Signaling System: 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.Phosphotyrosine: 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.Carcinoma, Non-Small-Cell Lung: 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.Receptors, Vascular Endothelial Growth Factor: 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.Fibroblast Growth Factor 7: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Mitogen-Activated Protein Kinase 3: 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.Epithelial Cells: 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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Down-Regulation: 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.Extracellular Signal-Regulated MAP Kinases: 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.Ligands: 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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mitogen-Activated Protein Kinase 1: 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.ras Proteins: 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 3.6.1.47.Gene Expression Regulation: 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.Apoptosis: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Reverse Transcriptase Polymerase Chain Reaction: 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.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.src-Family Kinases: 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.Mitogens: 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)Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Keratinocytes: 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.Vascular Endothelial Growth Factor Receptor-2: 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.Recombinant Fusion Proteins: 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.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Tumor Markers, Biological: 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.Proto-Oncogene Proteins c-cbl: 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.Peptides: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Receptor, Fibroblast Growth Factor, Type 2: 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).Cell Transformation, Neoplastic: 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.DNA: 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).GRB2 Adaptor Protein: 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).Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Receptor, IGF Type 1: 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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Receptor, Fibroblast Growth Factor, Type 1: 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.Adaptor Proteins, Signal Transducing: 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 enzymesPrecipitin Tests: 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.Up-Regulation: 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.Somatomedins: 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.Cell Survival: 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.RNA, Small Interfering: 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.Wound Healing: Restoration of integrity to traumatized tissue.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.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Fibroblast Growth Factor 10: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Models, Biological: 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.Gene Amplification: 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.Receptors, Transforming Growth Factor beta: 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Oncogene Proteins v-erbB: 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.Immunoblotting: 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.Protein Kinase C: 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.Vascular Endothelial Growth Factor Receptor-1: 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.Xenograft Model Antitumor Assays: 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.Protein Structure, Tertiary: 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.Connective Tissue Growth Factor: 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.COS Cells: 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).)Receptor, Platelet-Derived Growth Factor beta: A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.Proteins: 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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Neuregulins: A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor (RECEPTORS, ERBB-2). Multiple variant forms of NEUREGULINS occur due to alternative splicing of their mRNAs. The NEUREGULINS include products from the three known genes (NGR1; NGR2 and NGR3).Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Receptors, Estrogen: 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.PhosphoproteinsHead and Neck Neoplasms: 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)Membrane Proteins: 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.Receptors, Nerve Growth Factor: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Glioblastoma: 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.Blotting, Northern: 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.Culture Media, Serum-Free: 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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Receptors, Progesterone: Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Shc Signaling Adaptor Proteins: A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Transplantation, Heterologous: Transplantation between animals of different species.Neoplasm Proteins: 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.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Genes, erbB-2: The erbB-2 gene is a proto-oncogene that codes for the erbB-2 receptor (RECEPTOR, ERBB-2), a protein with structural features similar to the epidermal growth factor receptor. Its name originates from the viral oncogene homolog (v-erbB) which is a truncated form of the chicken erbB gene found in the avian erythroblastosis virus. Overexpression and amplification of the gene is associated with a significant number of adenocarcinomas. The human c-erbB-2 gene is located at 17q21.2.Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Glioma: 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)Brain Neoplasms: 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.Rats, Sprague-Dawley: 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.Receptor Cross-Talk: The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.Neuregulin-1: A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor (RECEPTOR, ERBB-2). It is a ligand for the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Variant forms of NEUREGULIN-1 occur through alternative splicing of its mRNA.Cell Line, Transformed: 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.Proto-Oncogene Proteins c-raf: A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.DNA Primers: 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.Neoplasms: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Prognosis: 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.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Insulin-Like Growth Factor Binding Proteins: A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)Promoter Regions, Genetic: 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.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.ADAM Proteins: A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Immunoenzyme Techniques: 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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Mice, Inbred BALB CMicroscopy, Fluorescence: 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.DNA-Binding Proteins: 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.Cell Adhesion: Adherence of cells to surfaces or to other cells.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.In Situ Hybridization: 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.Submandibular Gland: One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. (Stedman, 25th ed)Protein Transport: 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.Proto-Oncogene Proteins c-sis: 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.Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.RNA Interference: 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.Mice, Inbred C57BL

Immune responses to all ErbB family receptors detectable in serum of cancer patients. (1/11134)

Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-specific immunoprecipitates. Positive sera contained ErbB-specific antibodies of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in five of six patients. These findings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (2/11134)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. (3/11134)

Stimulation of the hepatocyte growth factor (HGF) receptor tyrosine kinase, Met, induces mitogenesis, motility, invasion, and branching tubulogenesis of epithelial and endothelial cell lines in culture. We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF. Gab1 is a member of the family of IRS-1-like multisubstrate docking proteins and, like IRS-1, contains an amino-terminal pleckstrin homology domain, in addition to multiple tyrosine residues that are potential binding sites for proteins that contain SH2 or PTB domains. Following stimulation of epithelial cells with HGF, Gab1 associates with phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP2. Met receptor mutants that are impaired in their association with Gab1 fail to induce branching tubulogenesis. Overexpression of Gab1 rescues the Met-dependent tubulogenic response in these cell lines. The ability of Gab1 to promote tubulogenesis is dependent on its pleckstrin homology domain. Whereas the wild-type Gab1 protein is localized to areas of cell-cell contact, a Gab1 protein lacking the pleckstrin homology domain is localized predominantly in the cytoplasm. Localization of Gab1 to areas of cell-cell contact is inhibited by LY294002, demonstrating that phosphatidylinositol 3-kinase activity is required. These data show that Gab1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3-kinase and the Gab1 pleckstrin homology domain as crucial for subcellular localization of Gab1 and biological responses.  (+info)

Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: potential interaction with epidermal growth factor receptor. (4/11134)

Tumor necrosis factor (TNF)-induced apoptosis can be inhibited by overexpression of specific tyrosine kinases or activation of tyrosine kinase cascades, suggesting potential antagonism between apoptotic and tyrosine kinase signaling processes. In this report, the effects of TNF on EGF receptor tyrosine phosphorylation in ME-180 cell variants selected for apoptotic sensitivity (Sen) or resistance (Res) to TNF, previously shown to differentially express EGFr, were examined. Prior to the onset of apoptosis, TNF caused a significant reduction in the level of EGFr tyrosine phosphorylation in Sen cells but mediated only limited suppression of EGFr tyrosine phosphorylation in apoptotically resistant Res cells. In vitro incubation of cellular membranes with TNF derived from Sen cells stimulated a resident protein tyrosine phosphatase (PTP) activity which was able to dephosphorylate EGFr or tyrosine phosphopeptides mimicking an EGFr autophosphorylation site. In membrane preparations, PTPIB complexed with tyrosine phosphorylated EGFr and this association was disrupted by TNF through an apparent stimulation of PTP activity and turnover of phosphotyrosine. Intrinsic enzymatic activity of PTP1B was 2-3-fold higher in Sen versus Res cell lysates and a family of PTP1B-related proteins with altered C-termini was found to be highly expressed in Sen cells but absent or expressed at reduced levels in Res cells. Cytoplasmic extracts of Sen cells contained PTP1B-like proteins and TNF incubation resulted in the time dependent accumulation of PTP1B-like proteins in Sen cells but did not effect these proteins in Res cells. Together, these results suggest that specific changes in expression and subcellular distribution of phosphotyrosine modulatory proteins may play a role in conveying intrinsic apoptotic sensitivity to TNF in some tumor cell types.  (+info)

An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling. (5/11134)

The ErbB2 receptor tyrosine kinase plays a critical role in a variety of developmental processes, and its aberrant activation may contribute to the progression of some breast and ovarian tumors. ASGP2, a transmembrane glycoprotein found on the surface of the highly metastatic ascites 13762 rat mammary adenocarcinoma cell line, is constitutively associated with ErbB2 in these cells and in mammary tissue from pregnant rats. Expression studies indicate that ASGP2 interacts directly and specifically with ErbB2 through one of its epidermal growth factor-like domains and that the co-expression of the two proteins in the same cell dramatically facilitates their direct stable interaction. Ectopic expression of ASGP2 in human melanoma tumor cells potentiates the response of endogenous ErbB2 to the neuregulin-1 growth factor. These observations point to a novel intramembrane mechanism for the modulation of receptor tyrosine kinase activity.  (+info)

Transforming growth factor-alpha acting at the epidermal growth factor receptor reduces infarct volume after permanent middle cerebral artery occlusion in rats. (6/11134)

Transforming growth factor-alpha (TGF-alpha) is a ligand for the epidermal growth factor (EGF) receptor (EGFR), and is more abundant than EGF in the brain. The authors studied whether administration of exogenous TGF-alpha into the brain can protect neurons against ischemia in a model of permanent middle cerebral artery (MCA) occlusion in the rat, and whether any effect of TGF-alpha was mediated by EGFR by administering 4,5-dianilinophthalimide (DAPH), a protein-tyrosine kinase inhibitor with high selectivity for EGFR. Rats received either TGF-alpha (10 or 25 ng), DAPH (100 ng), DAPH plus TGF-alpha (25 ng), or vehicle in the ipsilateral first ventricle. Drugs were administered twice: 30 minutes before and 30 minutes after MCA occlusion, and infarct volume was evaluated 24 hours later. Transforming growth factor-alpha at the dose of 25 ng caused a statistically significant reduction of infarct volume (60%) in relation to ischemic rats administered vehicle. This reduction was no longer seen when TGF-alpha was administered in combination with DAPH. The present results show that TGF-alpha can protect neurons from ischemic damage, and that this effect is mediated by EGFR. It is suggested that activation of EGFR-mediated intracellular signalling pathways contributes to the survival of neural cells susceptible to ischemic injury.  (+info)

Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas. (7/11134)

Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand-mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation.  (+info)

Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. (8/11134)

Epidermal growth factor receptor (EGFR) regulates the growth and progression of human transitional cell carcinoma (TCC) of the bladder. We have shown that therapy targeting EGFR inhibited the growth of human TCC established orthotopically in nude mice. The purpose of this study was to evaluate whether EGFR-directed therapy affects angiogenesis associated with the growth and metastasis of human TCC. We determined the cytostatic effect and the effect on production of angiogenic factors after in vitro treatment of the human TCC cell line 253J B-V with MAb C225, a chimerized monoclonal anti-EGFR antibody. The 253J B-V cells were implanted orthotopically into athymic nude mice, and established tumors (4 weeks) were treated with i.p. MAb C225. Expression of the angiogenic factors vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF) was evaluated by immunohistochemistry and in situ mRNA hybridization analyses and correlated with microvessel density evaluated after immunohistochemical staining with anti-CD31. In vitro treatment with MAb C225 inhibited mRNA and protein production of VEGF, IL-8, and bFGF by 253J B-V cells in a dose-dependent manner. MAb C225 therapy of nude mice with established TCCs growing orthotopically resulted in inhibition of growth and metastasis compared with controls (P <0.0005). VEGF, IL-8, and bFGF expression was significantly lower in treated tumors than in controls. The down-regulation of these angiogenic factors preceded the involution of blood vessels. These studies indicate that therapy with anti-EGFR MAb C225 has a significant antitumor effect mediated, in part, by inhibition of angiogenesis.  (+info)

Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.. ...
Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms.
Malignant peritoneal mesotheliomas (MPM) are rare tumors representing 20% of all malignant mesothelioma cases. The median survival for these tumors is less than a year, and like other peritoneal surface malignancies, this is due primarily to intra-abdominal recurrence and progression. Currently there is a paucity of information about the biology of these tumors and molecular perturbations that are involved in tumor formation. Elucidation of mutations and biological pathways active in these tumors may identify valuable prognostic markers, as well as facilitate the development of novel therapies. In this study, we investigate the predictive value of epidermal growth factor receptor (EGFR) mutations in achieving optimal resectability. Twenty-nine patients with MPM were evaluated at a single tertiary care center and their tumors were probed for point mutations in the catalytic TK domain of epidermal growth factor receptor (mut+). All specimens were examined for somatic mutations by polymerase chain ...
Glioblastoma is a highly aggressive primary brain tumor in which the majority of cancer cells are undifferentiated. One of the most common oncogenic drivers for this malignancy is the epidermal...
TY - JOUR. T1 - Role of proneuregulin 1 cleavage and human epidermal growth factor receptor activation in hypertonic aquaporin induction. AU - Herrlich, Andreas. AU - Leitch, Virginia. AU - King, Landon S.. PY - 2004/11/2. Y1 - 2004/11/2. N2 - Mammalian cells are confronted with changes in extracellular osmolality at various sites, including the aqueous layer above the lung epithelium. Hypertonic shock induces the activation of mitogen-activated protein kinases and the expression of a defined set of genes, including aquaporins. We investigated upstream components of the response to hypertonicity in lung epithelial cells and found that before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-β is cleaved and binds to human epidermal growth factor receptor 3 (HER3). The signaling is prevented by matrix metalloproteinase inhibition, inhibition of neuregulin 1-β binding to HER3, and inhibition of HER tyrosine kinase activity. ...
Monoclonal antibodies (MoAbs) were raised against epidermal growth factor (EGF) receptors on a human epidermoid carcinoma cell line, A431. Administration of anti-EGF receptor MoAbs inhibited tumor formation in athymic mice by A431 cells and by another epidermal carcinoma cell line, T222. When one of the same MoAbs was used in therapy against Li-7 (a human hepatoma) and HeLa cells (a cervical carcinoma), tumor growth was not affected. The number of EGF receptors on A431 cells was about 100-fold higher than on T222, Li-7, and HeLa cells, suggesting that the number of EGF receptors may not be an important determinant in suppressing tumor growth. Three anti-EGF receptor MoAbs were used in the present studies. MoAbs 528 (immunoglobulin G2a) and 225 (immunoglobulin G1) are capable of competing with EGF for receptor binding and inhibit proliferation of A431 cells in culture. The other MoAb, 455 (immunoglobulin G1), is incapable of blocking the binding of EGF to its receptors and has no effect on the ...
TY - JOUR. T1 - Disruption of ETV6 leads to TWIST1-dependent progression and resistance to epidermal growth factor receptor tyrosine kinase inhibitors in prostate cancer. AU - Tsai, Yuan Chin. AU - Zeng, Tao. AU - Abou-Kheir, Wassim. AU - Yeh, Hsiu Lien. AU - Yin, Juan Juan. AU - Lee, Yi Chao. AU - Chen, Wei Yu. AU - Liu, Yen Nien. PY - 2018/2/19. Y1 - 2018/2/19. N2 - Background: ETS variant gene 6 (ETV6) is a putative tumor suppressor and repressed by epidermal growth factor receptor (EGFR) signaling in prostate cancer. Since EGFR antagonists seem ineffective in castration-resistant prostate cancer (CRPC), we aim to study the role of ETV6 in the development of drug resistance. Methods: Etv6 target gene was validated by ChIP and promoter reporter assays. Correlation of ETV6 and TWIST1 was analyzed in human clinical datasets and tissue samples. Migration, invasion, and metastasis assays were used to measure the cellular responses after perturbation of ETV6 -TWIST1 axis. Proliferation and tumor ...
Title: Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and New Therapeutic Perspectives in Non Small Cell Lung Cancer. VOLUME: 12 ISSUE: 6. Author(s):Laura Bonanno, Antonio Jirillo and Adolfo Favaretto. Affiliation:Medical Oncology 2, Istituto Oncologico Veneto-IRCCS, Via Gattamelata, 64, 35128 Padova, Italy.. Keywords:EGFR, Tyrosine kinase inhibitors, resistance, mutations, amplifications, MET, VEGFR, NSCLC, Gefitinib, Erlotinib. Abstract: EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of ...
TY - JOUR. T1 - Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth factor receptor antibodies. T2 - Improved immunogene approach. AU - Chen, Jiabing. AU - Gamou, Shinobu. AU - Takayanagi, Atsushi. AU - Ohtake, Yuichiro. AU - Ohtsubo, Masafumi. AU - Shimizu, Nobuyoshi. PY - 1998. Y1 - 1998. N2 - We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with poly-L-lysine to form a gene delivery vehicle (designated Fab "immunoporter"). Within 12 hours, the β-galactosidase (β-gal) gene was transferred via the Fab immunoporter to virtually all of the nuclei of human squamous carcinoma A431 cells that overproduce the EGFR, and the β-gal enzyme activity was detected within 24 hours and retained for more than 3 days. ...
Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have
Epidermal growth factor (EGF) rapidly stimulates receptor autophosphorylation in A-431 cells. After 1 min the phosphorylated receptor can be identified at the plasma membrane using an anti-phosphotyrosine antibody. With further incubation at 37 degrees C, approximately 50% of the phosphorylated EGF receptor was internalized (t1/2 = 5 min) and associated with the tubulovesicular system and later with multivesicular bodies, but not the nucleus. During this period, there was no change in the extent or sites of phosphorylation. At all times the phosphotyrosine remained on the cytoplasmic side of the membrane, opposite to the EGF ligand identified by anti-EGF antibody. These data indicate that (a) the tyrosine-phosphorylated EGF receptor is internalized in its activated form providing a mechanism for translocation of the receptor kinase to substrates in the cell interior; (b) the internalized receptor remains intact for at least 60 min, does not associate with the nucleus, and does not generate any ...
After the intraportal injection of EGF, the EGF receptor (EGFR) is rapidly internalized into hepatic endosomes where it remains largely receptor bound (Lai et al., 1989. J. Cell Biol. 109:2751-2760). In the present study, we evaluated the phosphotyrosine content of EGFRs at the cell surface and in endosomes in order to assess the consequences of internalization. Quantitative estimates of specific radioactivity of the EGFR in these two compartments revealed that tyrosine phosphorylation of the EGFR was observed at the cell surface within 30 s of ligand administration. However, the EGFR was also highly phosphorylated in endosomes reaching levels of tyrosine phosphorylation significantly higher than those of the cell surface receptor at 5 and 15 min after EGF injection. A 55-kD tyrosine phosphorylated polypeptide (pyp55) was observed in association with the EGFR at the cell surface within 30 s of EGF injection. The protein was also found in association with the EGFR in endosomes as evidenced by ...
In the current study, we report on differences in outcome based on EGFR genotype after treatment with gefitinib or erlotinib in patients with NSCLC. A total of 36 eligible patients with EGFR mutations were identified. Of these, 32 (89%) patients had either an exon 19 deletion (n = 22) or the L858R point mutation (n = 10). This is the second study to compare patients with exon 19 deletions with those harboring an L858R point mutation and provides important independent validation to earlier observations (35). In a previously reported study, Riely et al. analyzed 34 NSCLC patients with either an exon 19 deletion (n = 23) or an L858R mutation (n = 11). Of these, 22 were treated with gefitinib and 12 were treated with erlotinib. The baseline characteristics of the patients in both studies are remarkably similar with respect to age, gender, smoking status, tumor histology, performance status, number of prior chemotherapy regimens, and EGFR-TKI administered.. Although the radiographic response rate in ...
This trial will investigate the efficacy and tolerability of epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, in combination with
This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type
TY - JOUR. T1 - Developmental regulation of epidermal growth factor receptor kinase in rat intestine. AU - Thompson, John F.. AU - Van Den Berg, Merlijn. AU - Stokkers, Pieter C.F.. PY - 1994/11. Y1 - 1994/11. N2 - Background/Aims: Intraluminal epidermal growth factor (EGF) may regulate intestinal growth and function. The ontogeny, localization, and phosphorylation of the EGF receptor in rat small intestine were studied. Methods: EGF-receptor phosphorylation was assayed by antiphosphotyrosine Western blot after EGF administration in vivo and EGF incubation to everted sacs in vitro. EGF-receptor abundance and localization were assayed by Western blot and immunofluorescence using anti-EGF-receptor antibodies. Results: In vivo, orogastric EGF enhanced EGF-receptor phosphorylation in newborn rat jejunum and liver. However, intraluminal EGF had no effect on EGF-receptor phosphorylation in adult intestine or liver. In vitro, mucosal EGF stimulated a fourfold increase in EGF-receptor phosphorylation in ...
Title: Targeting Epidermal Growth Factor Receptor in Solid Tumors: Critical Evaluation of the Biological Importance of Therapeutic Monoclonal Antibodies. VOLUME: 16 ISSUE: 29. Author(s):Ch. Gialeli, D. Kletsas, D. Mavroudis, H. P. Kalofonos, G. N. Tzanakakis and N. K. Karamanos. Affiliation:Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece.. Keywords:Epidermal growth factor receptor, solid tumors, colorectal cancer, anti-EGFR therapy, monoclonal antibodies, cetuximab, panitumumab. Abstract: Numerous cellular pathways have a significant impact in the growth and metastatic potential of tumors. Essential element of such pathways is the epidermal growth factor receptor (EGFR), a member of the HER family of receptor tyrosine kinases. One of the most important issues in cancer, which attracted the attention of clinical oncologists, is the potential use of targeted therapies. EGFR signaling pathway is implicated in the control of cell survival, ...
Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen,
Background Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. In patients with ccRCC several prognostic markers have been suggested, enclosing epidermal growth factor receptor (EGFR) expression and chromosome 7 polysomy (C7p). Cancer cells addicted to EGFR bear activated mutations in the EGFR gene, and these mutations are useful in predicting susceptibility of ccRCC to EGFR inhibitors. The aim of this study was to evaluate the prognostic value of EGFR overexpression and C7p.. Patients and methods Archival specimens, coupled with clinical and survival data of 34 patients (20 men, 14 women, median age 58, range 42-79 years) who had undergone radical nephrectomy for ccRCC were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) specimens were sections of formalin-fixed paraffin-embedded tissue. EGFR expression was detected as membranous and cytoplasmic staining of neoplastic cells > 1%, and a ratio between ...
TY - JOUR. T1 - IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. AU - Shim, Jae Jeong. AU - Dabbagh, Karim. AU - Ueki, Iris F.. AU - Dao-Pick, Trang. AU - Burgel, Pierre Regis. AU - Takeyama, Kiyoshi. AU - Tam, Dominic Cheng Wei. AU - Nadel, Jay A.. PY - 2001/1. Y1 - 2001/1. N2 - Mucus hypersecretion contributes to the morbidity and mortality in acute asthma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophils is implicated in interleukin (IL)-13-induced mucin expression in GC. Treatment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-induced GC metaplasia dose dependently and completely. Instillation of IL-13 also induced tumor necrosis factor-α protein expression, mainly in infiltrating neutrophils. Control airway epithelium contained few ...
INTRODUCTION. Glioblastoma (GBM) is the most common intracranial cancer in adults but despite recent advances in therapy the overall survival remains about 20 months. The epidermal growth factor receptor variant III (EGFRvIII) is a truncated, constitutively active, and highly oncogenic form of the EGFR expressed on approximately 30% of GBMs. Sym004 is a recombinant IgG1 antibody mixture consisting of two antibodies against domain III of the epidermal growth factor receptor (EGFR). Like anti-EGFR monoclonal antibodies, Sym004 inhibits cancer cell growth and survival by blocking ligand-binding and receptor signaling. However, unlike the monoclonal antibodies, Sym004 induces a rapid and efficient internalization and degradation of the EGFR. Here, we examine whether the more efficient removal of the EGFR and the constitutive active EGFRvIII by Sym004 would translate into increased tumor growth inhibition of EGFRvIII GBM xenografts.. METHODS. Both subcutaneous (sc) and intracranial (ic) adult brain ...
The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly
Supplementary Material for: Role of Epidermal Growth Factor Receptor Expression on Patient Survival in Pancreatic Cancer: A Meta-Analysis
Close, J. L., Liu, J., Gumuscu, B. and Reh, T. A. (2006), Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina. Glia, 54: 94-104. doi: 10.1002/glia.20361 ...
The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients and to apply logistic regression analysis to investigate the factors associated with EGFR gene mutation to provide data for the treatment of NSCLC. Paraffin tissue, bronchoscopy or pleural effusion specimens were collected from 176 NSCLC patients following pathological diagnosis. The EGFR gene exon 19 delL747-S75linss and delL747-S752ins deletion mutations, and the exon 20 T790M and exon 21 L858R mutations were identified using amplification refractory mutation system analysis. The clinical data and laboratory results of the patients were collected, and the total mutation rate of the EGFR gene in exons 19, 20 and 21 in the 176 NSCLC patients was found to be 48.3% (85/176). In addition, the EGFR gene mutation rate in adenocarcinoma was found to be significantly higher than that in squamous cell and large cell carcinoma (χ²=12.454; ...
The epidermal growth factor receptor (EGFR) is a widely expressed Ag that is successfully targeted in tumor patients by mAbs or tyrosine kinase inhibitors. A clinical study in non-small cell lung cancer patients demonstrated a positive correlation between EGFR expression levels and the therapeutic efficacy of the EGFR mAb cetuximab. However, the impact of EGFR expression on the different mechanisms of action (MoAs) triggered by the EGFR mAb has not been defined. In this study, BHK-21 cells were stably transfected to express different EGFR levels, which were quantified by immunofluorescence and immunohistochemistry and compared with EGFR levels of clinical non-small cell lung cancer samples. These cells were used to systematically investigate the impact of target Ag expression levels on Fab- or Fc-mediated MoAs of EGFR mAb. A negative correlation between EGFR levels and potency of Fab-mediated MoA was observed. Interestingly, Ab-dependent cell-mediated cytotoxicity (ADCC) by NK cells, monocytes, ...
TY - JOUR. T1 - Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. AU - Lipton, Allan. AU - Leitzel, Kim. AU - Ali, Suhail M.. AU - Carney, Walter. AU - Platek, Greg. AU - Steplewski, Klaudia. AU - Westlund, Ron. AU - Gagnon, Robert. AU - Martin, Anne Marie. AU - Maltzman, Julie. PY - 2011/11/1. Y1 - 2011/11/1. N2 - BACKGROUND: Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first-line lapatinib monotherapy. METHODS: The EGF20009 study ...
TY - JOUR. T1 - Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer. T2 - Results of the randomized phase II CHER-LOB study. AU - Guarneri, Valentina. AU - Frassoldati, Antonio. AU - Bottini, Alberto. AU - Cagossi, Katia. AU - Bisagni, Giancarlo. AU - Sarti, Samanta. AU - Ravaioli, Alberto. AU - Cavanna, Luigi. AU - Giardina, Giovanni. AU - Musolino, Antonino. AU - Untch, Michael. AU - Orlando, Laura. AU - Artioli, Fabrizio. AU - Boni, Corrado. AU - Generali, Daniele Giulio. AU - Serra, Patrizia. AU - Bagnalasta, Michela. AU - Marini, Luca. AU - Piacentini, Federico. AU - DAmico, Roberto. AU - Conte, PierFranco. PY - 2012/6/1. Y1 - 2012/6/1. N2 - Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II ...
Epidermal growth factor receptors (EGF-Rs) are expressed at increasing levels on mouse preimplantation embryos. Immunofluorescence assays were used to show that unfertilized eggs and 2-cell embryos have a very low level of reactivity to antimouse EGF-R antibodies, but by the 4-cell stage and later t …
TY - JOUR. T1 - Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. AU - Carey,Lisa A.. AU - Berry,Donald A.. AU - Cirrincione,Constance T.. AU - Barry,William T.. AU - Pitcher,Brandelyn N.. AU - Harris,Lyndsay N.. AU - Ollila,David W.. AU - Krop,Ian E.. AU - Henry,Norah Lynn. AU - Weckstein,Douglas J.. AU - Anders,Carey K.. AU - Singh,Baljit. AU - Hoadley,Katherine A.. AU - Iglesia,Michael. AU - Cheang,Maggie Chon U.. AU - Perou,Charles M.. AU - Winer,Eric P.. AU - Hudis,Clifford A.. PY - 2016/2/20. Y1 - 2016/2/20. N2 - Purpose Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (PCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, ...
Targeted molecular therapy offers an exciting, new approach to treat human malignancy (1) and represents a fundamental change in cancer therapeutics (2) . Current treatment relies on cytotoxic drugs that, for the most part, lack specificity for tumor cells. A better understanding of the molecular pathogenesis of cancer has identified targets for therapeutic intervention that are specific against tumor cells and hence may reduce toxicity commonly associated with adjuvant treatment. The success of the TKI STI-571 in early clinical trials for the treatment of chronic myeloid leukemia (3) and gastrointestinal stromal tumors (4) highlights the unique potential for novel therapy based on specific molecular abnormalities present in a human cancer.. The EGFR3 pathway provides an attractive target for molecular therapy of HNSCC. Most work has focused on the use of anti-EGFR antibody preparations. Tumor proliferation in cell culture and tumor xenografts in athymic mice have been inhibited by these ...
Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR) expression and activation, causing goblet-cell metaplasia from Clara cells by a process of cell differentiation. These cells are also believed to be the cells of origin of non-small-cell lung cancer, but this occurs via cell multiplication. The mechanisms that determine which pathway is chosen are critical but largely unknown. Although no effective therapy exists for hypersecretion at present, the EGFR cascade suggests methods for effective therapeutic intervention.
... with a gene situated in the brief arm of chromosome 7. inhibitors (p=0.032). The outcomes of the existing study could be found in decision-making relating to the treating individuals with traditional EGFR exon mutations. solid course="kwd-title" Keywords: lung adenocarcinoma, traditional EGFR mutations, micropapillary design, tyrosine kinase inhibitors Intro Lung cancer may be the most popular reason behind cancer-related death world-wide, with non-small cell lung malignancy (NSCLC) being the most frequent type [1, 2]. Improved knowledge of hereditary alteration in lung malignancy has resulted in the development of several onco-targeted medicines and significant accomplishments [3C5]. Activating mutations of epidermal development element receptor (EGFR) are recognized in about 20% of lung adenocarcinomas in Traditional western countries [6] and 40%C60% of lung adenocarcinomas in East Asia [7C9]. These ...
Aida, S., et al., Distribution of epidermal growth factor and epidermal growth factor receptor in human lung: immunohistochemical and immunoelectron-microscopic studies. Respiration, 1994. 61(3):161-166.. Allahverdian, S., et al., Sialyl Lewis X modification of the epidermal growth factor receptor regulates receptor function during airway epithelial wound repair. Clin Exp Allergy, 2010. 40(4):607-618.. Blanchet, S., et al., Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells. Am J Resp Cell Mol Biol, 2004. 30(4):421-427.. Burgel, P.-R. and J.A. Nadel, Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Resp J, 2008. 32(4):1068-1081.. Ciardiello, F., and Tortora, G. (2008). EGFR antagonists in cancer treatment. N Engl J Med, 2008. 358(11):1160-1174.. Casalino-Matsuda, S.M., et al., Role of hyaluronan and reactive oxygen species in tissue kallikrein-mediated epidermal growth factor receptor activation in human ...
Specific, high affinity receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have been demonstrated in human breast cancer cells. In addition, 1,25-(OH)2D3 has been shown to inhibit replication in some human breast cancer cell lines, although the mechanism(s) of this anti-tumor activity remain undefined. There is currently considerable interest in the role of autocrine growth factors in the control of breast cancer cell proliferation and the effects of steroid hormones on their production, receptor binding, and action. Since the epidermal growth factor (EGF) receptor mediates the effects of both EGF and the autocrine growth factor, alpha-transforming growth factor, we investigated the effect of 1,25-(OH)2D3 on EGF receptor levels in several human breast cancer cell lines. Preincubation of T-47D cells with 1,25-(OH)2D3 for 24 h resulted in a significant concentration-dependent decline in the specific binding of [125I]EGF. The effect was observed when EGF binding was assayed at either 0 or 37 degrees C,
Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PI3 kinase dependent pathway
The vaccine rindopepimut appears to benefit patients with epidermal growth factor receptor variant III mutation (EGFRvIII) in glioblastoma with regard to progression-free survival (PFS) and overall survival (OS).
International Scholarly Research Notices is a peer-reviewed, Open Access journal covering a wide range of subjects in science, technology, and medicine. The journals Editorial Board as well as its Table of Contents are divided into 108 subject areas that are covered within the journals scope.
We read with great interest the article by Arevalo-Perez et al, describing the potential value of T1-weighted dynamic contrast-enhanced MR imaging (DCE-MR imaging) as a biomarker for epidermal growth factor receptor variant III (EGFRvIII) mutation in patients with glioblastoma (GBM).
TY - JOUR. T1 - Src family kinases negatively regulate platelet-derived growth factor α receptor-dependent signaling and disease progression. AU - Rosenkranz, Stephan. AU - Ikuno, Yasushi. AU - Leong, Fee Lai. AU - Klinghoffer, Richard A.. AU - Miyake, Sachiko. AU - Band, Hamid. AU - Kazlauskas, Andrius. PY - 2000/3/31. Y1 - 2000/3/31. N2 - We tested the hypothesis that Src family kinases (SFK) contribute to c- Cbl-mediated degradation of the platelet-derived growth factor (PDGF) α receptor (αPDGFR). Using either a receptor mutant that does not engage SFKs (F72174), or cells that that lack SFKs, we found that SFKs contributed to degradation of the αPDGFR. Overexpression of c-Cbl also reduced the receptor half-life, but only if the receptor was able to engage SFKs. In cultured cells, prolonging the half-life of the receptor correlated with enhanced signaling and more efficient S phase entry, whereas accelerating receptor degradation had the opposite effect. Consistent with these tissue ...
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Currently, there is no standard salvage regimen after the failure of cisplatin-based chemotherapy for advanced urothelial carcinoma. Many novel agents have been developed and have shown modest activity in urothelial carcinoma. With the advancement of molecular biology and a deeper understanding of the pathogenesis of urothelial carcinoma, new approaches for treating patients using molecularly targeted therapies have emerged. Previous studies have shown that the over-expression of epidermal growth factor receptor (EGFR) predicts poor survival and stage progression [4, 5]. EGFR is more strongly expressed in invasive tumors (pT2-T4) and high-grade tumors than in superficial or low-grade tumors [4]. However, mutations within the kinase domain and truncations of the EGFR are rarely seen in bladder cancer, and they have emerged as attractive therapeutic targets. Cetuximab (an EGFR inhibitor) is a chimeric human/mouse monoclonal antibody that prevents dimerization by binding to the extracellular domain ...
The EGFR TKI erlotinib was shown to result in increased survival in previous clinical trials when used as monotherapy in previously treated patients with advanced NSCLC [30]. Toxicity to erlotinib is markedly lower than many alternative pharmacologic treatments, and would clearly be a preferred therapeutic option if survival was shown to be equivalent or better than treatment with other second line agents. Since only a fraction of patients respond to such therapy, a priori identification of responders could have a vast effect on survival. Many clinical parameters which have been shown to correlate with response to EGFR TKIs, including smoking history, gender, ethnicity, and tumor histology. Additionally, EGFR expression levels, phosphorylation status of EGFR, and mutations within the kinase domain [22, 28, 31] also correlate with sensitivity to some degree. While each of these predictors of response result in some overlap, potential responders to EGFR targeted therapeutics may be overlooked. In ...
Epidermal growth factor receptor signalling regulates ommatidial rotation during Drosophila eye development [Elektronische Ressource] / presented by Konstantin Gängel : Dissertationsubmitted to theCombined Faculties of the Natural Sciences and for Mathematicsof the Ruperto-Carola University of Heidelberg, Germanyfor the degree ofDoctor of Natural Sciencepresented byDiplombiologen Konstantin Gängelborn in HeidelbergOral-examination: 25. Mai 2005Epidermal growth factor receptor signalling regulates ommatidialrotation during Drosophila eye developmentReferees: Prof
Classic activating mutations in the EGFR tyrosine kinase domain, such as L858R and deletions in exon 19, have been strongly associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). Other mutations, e.g. T790M, show drug resistance. Detection of EGFR mutations has become an important issue for therapeutic decision-making in NSCLC. The clinical significance of uncommon EGFR mutations, however, remains poorly understood. The present study describes clinical outcomes of 6 patients with uncommon EGFR mutations, receiving TKI.. ...
TY - JOUR. T1 - Mechanisms and overcome of acquired resistance to EGFR tyrosine kinase inhibitors. AU - Soh, Junichi. AU - Toyooka, Shinichi. AU - Ueno, Tsuyoshi. AU - Miyoshi, Shinichiro. PY - 2012/4. Y1 - 2012/4. N2 - Development of effective therapies for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, which account for approximately 40% of lung adenocarcinoma patients in Japan, is important to improve the clinical outcome of NSCLC. EGFR-mutant NSCLCs are sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and elucidating the binding affinity of adenosine triphosphate (ATP) and EGFR-TKI to wild type or mutant EGFR helps our understanding of the mechanisms of resistance to EGFR-TKI. The mechanisms of acquired resistance to EGFR-TKIs are broadly classified into two categories: 1) secondly acquired EGFR mutations including T790M and 2) "oncogene kinase switch" such as MET gene amplification. To overcome the acquired resistance, it is ...
Growth factors transmit biological signals for the stimulation of cell growth and their stimulation may be involved in turnourigenesis. It is therefore of great importance to understand growth factor receptor reactions in response to stimuli such as calcium depletion or ultraviolet radiation, which normal human cells are invariably exposed to during their growth cycle. We have studied human skin cells i.e. fibroblasts, lceratinocytes and melanocytes and their growth factor receptor expression on the surface of cells, reactions in the plane of the cell membrane, intracellular trafficlcing, and gene expression after exposure to their ligand, serum, UVB radiation and calcium depletion. We have used Fluorescence recovery after photo bleaching (FRAP) to assess receptor characteristics in cell membranes, confocal laser scanning microscopy to visualize receptor internalization, Ratio imaging for calcium studies, Northern blot for detection of the gene for the epidermal growth factor receptor (EGF-R) ...
Inhibition of epidermal growth factor receptor (EGFR) signaling sensitizes human malignant glioma cells to death ligand-induced apoptosis. However, tumor cells may compensate the loss of EGFR signaling by activation of the type 1 insulin-like growth factor receptor (IGF-1R). We here report that anta …
The phosphorylated epidermal growth factor receptor (EGFR) initiates intracellular signaling processes that regulate cell growth, survival, and migration, and disregulated EGFR-mediated signaling occurs in many cancers. While the processes that lead to EGFR activation and phosphorylation have been studied in detail, quantitative aspects of the spatiotemporal regulation of EGFR by protein tyrosines phosphatases (PTPs) are not well understood. To begin to address this, we developed a new compartmentalized mechanistic model of EGFR phosphorylation dynamics and used it to interpret quantitative biochemical measurements to show that EGFR is dephosphorylated at the plasma membrane and in the cell interior with a time scale that is small compared to the time scales for EGFR internalization. By expanding our computational model and experimental data set, we went on to demonstrate that EGFR dephosphorylation at the plasma membrane surprisingly does not affect phosphorylation-dependent EGFR internalization
Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population. We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C|T, 142285G|A, 162093G|A, 181946C|T and 187114T|C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls. Of the 5 polymorphisms, the 181946C|T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45-0.88, P = 0.007). When the analyses were stratified by smoking status, the
Epidermal growth factor receptor[edit]. An example of RTKs that undergo autophosphorylation is the Epidermal Growth Factor ... 1: Activation of the Epidermal Growth Factor Receptor by autophosphorylation. Adapted from Pecorino (2008)[1] ... Insulin receptors[edit]. Another example is the binding of insulin to insulin receptors. Once released into the bloodstream ... This receptor is a protein with an (αβ)2 quaternary structure. The two large α-subunits are extracellular, while the smaller β- ...
Herbst RS (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, ... Epidermal growth factor (EGF). *Various enzymes; there are three major enzymes found in saliva: *α-amylase (EC3.2.1.1), or ... Researchers at the University of Florida at Gainesville have discovered a protein called nerve growth factor (NGF) in the ... It is the liquid medium in which chemicals are carried to taste receptor cells (mostly associated with lingual papillae). ...
Inhibitors of Epidermal growth factor receptor (EGFR) *tyrosine kinase inhibitors (TKI's):[9] *erlotinib (Tarceva)[10][ ... Riely GJ, Politi KA, Miller VA, Pao W (December 2006). "Update on epidermal growth factor receptor mutations in non-small cell ... Shigematsu H, Gazdar AF (January 2006). "Somatic mutations of epidermal growth factor receptor signaling pathway in lung ... "Epidermal growth factor receptor mutations in small cell lung cancer". Clinical Cancer Research. 14 (19): 6092-6. doi:10.1158/ ...
Herbst RS (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, ... Epidermal growth factor (EGF) results in cellular proliferation, differentiation, and survival.[21] EGF is a low-molecular- ... They secrete hydrochloric acid (HCl) and intrinsic factor.[10] The pyloric glands are located in the antrum of the pylorus. ... The human stomach can "taste" sodium glutamate using glutamate receptors[23] and this information is passed to the lateral ...
October 2003). "Aldosterone stimulates epidermal growth factor receptor expression". J. Biol. Chem. 278 (44): 43060-66. doi: ... and also by epidermal growth factor (EGF), which is a target of the signaling pathway activated by aldosterone[35] ... Many of these remodelling effects seem to be mediated by transforming growth factor beta (TGF-beta), which is a common ... Binding to beta-1 receptors in the myocardium increases the heart rate and makes contractions more forceful in an attempt to ...
Among the overexpressed targets are members of the epidermal growth factor receptor (EGFR) family, transmembrane proteins with ... "Epidermal growth factor receptor inhibition strategies in oncology". Endocrine-Related Cancer. 11 (4): 689-708. doi:10.1677/erc ... "Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases ... Such hormone receptors can be detected by immunohistochemistry.[13] Imatinib, an intracellualar tyrosine kinase inhibitor, was ...
It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ... Erlotinib is an epidermal growth factor receptor inhibitor (EGFR inhibitor). The drug follows Iressa (gefitinib), which was the ... Raymond E, Faivre S, Armand J (2000). "Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy". ... Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and ...
The EGFR is receptor tyrosine kinase which binds multiple growth factors including EGF (epidermal growth factor) and other ... "Tumor growth modulation by a monoclonal antibody to the epidermal growth factor receptor: immunologically mediated and effector ... Matuzumab binds to epidermal growth factor receptor (EGFR) on the outer membrane of normal and tumor cells. The matuzumab ... It binds to the epidermal growth factor receptor (EGFR) with high affinity.[1] The mouse monoclonal antibody (mAb425) from ...
... epidermal growth factor; EGFR, epidermal growth factor receptor; MoAbs, monoclonal antibodies; VEGF, vascular endothelial ... factor for BPA in skin of 2.5. A relative biological effectiveness (RBE) or CBE factor of 3.2 has been used in all tissues for ... growth factor. The major challenge in the development of boron delivery agents has been the requirement for selective tumor ... Biological weighting factors have been used in all of the recent clinical trials in patients with high grade gliomas, using ...
Hazan RB, Norton L (April 1998). "The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin ... "Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling". Cancer Research. 68 (13 ... De Craene B, Gilbert B, Stove C, Bruyneel E, van Roy F, Berx G (July 2005). "The transcription factor snail induces tumor cell ... positive regulation of transcription factor import into nucleus. • pituitary gland development. • response to toxic substance. ...
This is accomplished through fusion of epidermal growth factor(EGF) with SubAB's A subunit. Cancer cells that express receptors ... The glycan receptor for SubAB usually ends with an α2-3-linked N-Glycolylneuraminic acid (Neu5Gc). SubAB has an A subunit where ... The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit ... This B subunit ring is also capable of binding to a receptor on the surface of the host cell. Without the B subunits, the A ...
Osherov N, Gazit A, Gilon C, Levitzki A (1993). "Selective inhibition of the epidermal growth factor and HER2/neu receptors by ... which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). ... "Kinetics of inhibition by tyrphostins of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a ... I dose-escalation study of 5-day intermittent oral lapatinib therapy in patients with human epidermal growth factor receptor 2- ...
Nimotuzumab is an inhibitor of epidermal growth factor receptor (EGFR), which is over-expressed in many cancers. Nimotuzumab is ... "The two determining factors underlying the crisis are well known. One is the dissolution of the Soviet Union and the socialist ... There are other factors beside the embargo explaining the lack of imports, in particular Cuba's lack of hard currency. Those ... Here, students are exposed to medicine and the social, economical, and political factors that influence health.[52] At primary ...
"Microfluidics-assisted fluorescence in situ hybridization for advantageous human epidermal growth factor receptor 2 assessment ... Fluorescent signal strength depends on many factors such as probe labeling efficiency, the type of probe, and the type of dye. ...
May 2003). "Real-Time Vital Optical Imaging of Precancer Using Anti-Epidermal Growth Factor Receptor Antibodies Conjugated to ... Finally pigs have similar physical and molecular responses to various growth factors.. .mw-parser-output cite.citation{font- ... Pig skin is structurally similar to human epidermal thickness and dermal-epidermal thickness ratios. Pigs and humans have ... and pig skin and human skin have similar physical responses to various growth factors.[2][3] ...
Gefitinib(Iressa) and Erlotinib (Tarceva) are epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors used for non- ... "Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer" ... Resistance to selective estrogen receptor modulator drugs[edit]. Selective estrogen receptor modulators (SERMs) are a commonly ... Interference/cross-talk with growth factor signaling pathways such as EGFR/HER2 ...
"The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense ... "Expression of the epidermal growth factor seven-transmembrane member CD97 correlates with grading and staging in human oral ... In the case of CD97 the N-terminal domains consist of alternatively spliced epidermal growth factor (EGF)-like domains. ... Several treatments reduce CD97 expression in tumor cells such as cytokine tumor growth factor (TGF)β as well as the compounds ...
The first identified virokine was an epidermal growth factor-like protein found in myxoma viruses. Much of the early work on ... growth factors, or complement regulators; the term viroceptor is sometimes used if the proteins resemble cellular receptors. A ... Viroceptors mimic host receptors and thus divert signaling molecules from finding their targets. Cytokine-binding proteins bind ... Alcami, A (January 2003). "Viral mimicry of cytokines, chemokines and their receptors". Nature Reviews. Immunology. 3 (1): 36- ...
"Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Reverses Mesenchymal to Epithelial Phenotype and Inhibits Metastasis ... A large number of IBC cases present as triple negative breast cancer (TNBC). Similar to TNBC as opposed to estrogen receptor- ... Estrogen and progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly ... Van Laere, S. J (2006). "Nuclear Factor-κB Signature of Inflammatory Breast Cancer by cDNA Microarray Validated by Quantitative ...
"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network ...
"Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors ... Cancerous cells overexpress a number of proteins, including growth factor receptors, such as EGFR, or signal transduction ... Hsp90 stabilizes various growth factor receptors and some signaling molecules including PI3K and AKT proteins. Hence inhibition ... tumor necrosis factor receptors (TNFR) and nuclear factor-κB (NF-κB) function." Also, Hsp90 participates in many key processes ...
"The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... CDK8 binds to and/or phosphorylates several transcription factors, which can have an activating or inhibitory effect on ... interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor ...
It is mainly used to treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[5] ... Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor (EGFR) via a Michael addition (IC50 = ... Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive ... and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first ...
"Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living ... T cell receptor signaling pathway. • T cell activation. • regulation of catalytic activity. • Rho protein signal transduction. ... Fc-gamma receptor signaling pathway involved in phagocytosis. • protein complex assembly. • actin filament organization. • ... MBInfo - WASP and other Nucleation Promotion Factors. *GeneReviews/NIH/NCBI/UW entry on WAS-Related Disorders including Wiskott ...
2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling ... Tyrosine-protein phosphatase non-receptor type 18 is an enzyme that in humans is encoded by the PTPN18 gene.[5][6] ... PTPN18, BDP1, PTP-HSCF, protein tyrosine phosphatase, non-receptor type 18. External IDs. MGI: 108410 HomoloGene: 74971 ... PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, ...
High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne.[42] Both ... C. acnes' ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 ... These peels only affect the epidermal layer of the skin and can be useful in the treatment of superficial acne scars as well as ... Another common factor is the excessive growth of the bacterium Cutibacterium acnes, which is present on the skin.[15] ...
Polypeptide growth factors have been recognized as important determinants In the regulation of cellular proliferation and ... Epidermal Growth Factor Receptor Human Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Kinase Protein ... Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 26 ... C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated protein-kinase ...
The development and clinical application of inhibitors that target the epidermal growth factor receptor (EGFR) provide ... Epidermal growth factor receptor mutations in lung cancer Nat Rev Cancer. 2007 Mar;7(3):169-81. doi: 10.1038/nrc2088. ... The development and clinical application of inhibitors that target the epidermal growth factor receptor (EGFR) provide ...
Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a ... member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have ... Epidermal Growth Factor Receptor in Pancreatic Cancer. Melissa Oliveira-Cunha 1,* , William G. Newman 2. ... Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a ...
Epidermal growth factor receptor (EGFR) inhibitor. Additional Keywords : COLORECTAL CANCER, Epidermal growth factor receptor ( ... Pharmacological Actions : Epidermal growth factor receptor (EGFR) inhibitor, NF-kappaB Inhibitor, Tumor Necrosis Factor (TNF) ... 59 Abstracts with Epidermal growth factor receptor (EGFR) inhibitor Research. Filter by Study Type. Animal Study. ... Pharmacological Actions : Epidermal growth factor receptor (EGFR) inhibitor. Additional Keywords : Chemotherapeutic Synergy: ...
Effective Inhibition of the Epidermal Growth Factor/Epidermal Growth Factor Receptor Binding by Anti-Epidermal Growth Factor ... Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and amphiregulin are structurally and functionally ... Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. G D Plowman, G S Whitney, M G ... Role of extracellular subdomains of p185c-neu and the epidermal growth factor receptor in ligand-independent association and ...
Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers.. Shigematsu H1, Gazdar AF. ... Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers have ... Epidemiological studies to identify possible carcinogenic factor(s) affecting different subpopulations are also of interest. In ... it is not the sole factor, and evidence is accumulating that EGFR gene amplification, other members of the EGFR family (HER2, ...
Epidermal growth factor receptor (EGFR) content was determined by a radioligand receptor assay in 140 primary laryngeal ... Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma.. Maurizi M1, Almadori G, ...
epidermal growth factor;. EGF-Ct,. EGF with carboxyl terminus;. EGFR,. EGF receptor;. HMEC,. human mammary epithelial cells;. ... The epidermal growth factor receptor (EGFR) plays an important role during development. Knockout of the EGFR gene results in ... Ligands that activate the epidermal growth factor receptor (EGFR) are synthesized as membrane-anchored precursors that appear ... Metalloprotease-mediated ligand release regulates autocrine signaling through the epidermal growth factor receptor. Jianying ...
The author discusses three new studies in PLoS Medicine that shed light on the mechanisms involved in apoptosis triggered by EGFR kinase inhibitors.
Copy of Epidermal Growth Factor Receptor (EGFR). No description by Brendan Vonick. on 4 December 2012 ...
Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor of the ErbB family, and the biological receptor of EGF and ... J. R. Grandis and D. J. Tweardy, "Elevated levels of transforming growth factor α and epidermal growth factor receptor ... "Asynchronous modulation of transforming growth factor α and epidermal growth factor receptor protein expression in progression ... Epidermal Growth Factor Receptor Protein: A Biological Marker for Oral Precancer and Cancer. Ashish Mahendra,1 Balasundari ...
"Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor". Growth ... "Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor". Biochemistry. ... The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor ... "Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor". Growth ...
Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. ... Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. ... Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent ...
... activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. ... The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. ... Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. ... Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular ...
... and its ligands have been long recognized as centrally involved in the growth and repair process of epithelia, as well as in ... The epidermal growth factor receptor (EGFR) and its ligands have been long recognized as centrally involved in the growth and ... Pastore S, Mascia F, Mariani V, Girolomoni G (2002) Epidermal growth factor receptor ligands and tumor necrosis factor-alpha ... Mendelsohn J, Baselga J (2006) Epidermal growth factor receptor targeting in cancer. Semin Oncol 33:369-385PubMedGoogle Scholar ...
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. ... Epidermal growth factor receptor KINASE DOMAIN 9606 2.7.10.1 , Details 41 5C8N 1 A Epidermal growth factor receptor 9606 2.7. ... Epidermal growth factor receptor 694-1022 9606 2.7.10.1 , Details 103 5C8M 1 A Epidermal growth factor receptor 9606 2.7.10.1 ... Epidermal growth factor receptor Residues 702-1016 9606 2.7.10.1 , Details 51 5HIC 1 A Epidermal growth factor receptor 9606 ...
ERBB; ERBB1; Erb-B2 receptor tyrosine kinase 1; Erythroblastic leukemia viral (V-Erb-B) oncogene homolog (Avian); HER1; Proto- ... oncogene C-ErbB-1; Receptor tyrosine-protein kinase ErbB-1 The... ... Heparin-binding epidermal growth factor-like growth factor (HB- ... The epidermal growth factor receptor (EGFR, also known as ErbB1) is the first of four members of the ErbB lineage of receptor ... A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results ...
Binding of epidermal growth factor (EGF) to its receptor leads to receptor dimerization, assembly of protein complexes, and ... Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6 Message Subject. (Your Name) has ... Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6. By Yonathan Lissanu Deribe, Philipp ... Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6. By Yonathan Lissanu Deribe, Philipp ...
Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. ... Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent ... Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. ... Epidermal growth factor receptor substrate 15Add BLAST. 896. Amino acid modifications. Feature key. Position(s). Description ...
Compare epidermal growth factor receptor ELISA Kits from antibodies-online from leading suppliers on Biocompare. View ... Epidermal Growth Factor Receptor (P-EGFR) ELISA Kit antibodies-online *Detection Target: Epidermal Growth Factor Receptor (P- ... Epidermal Growth Factor Receptor (P-EGFR) ELISA Kit antibodies-online *Detection Target: Epidermal Growth Factor Receptor (P- ... Epidermal Growth Factor Receptor (P-EGFR) ELISA Kit antibodies-online *Detection Target: Epidermal Growth Factor Receptor (P- ...
epidermal growth factor receptor. News tagged with epidermal growth factor receptor. * Date 6 hours 12 hours 1 day 3 days all ... with epidermal growth factor receptor ... ...
Close, J. L., Liu, J., Gumuscu, B. and Reh, T. A. (2006), Epidermal growth factor receptor expression regulates proliferation ... Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina. ...
Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, ... combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the ... Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and ... Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and ...
... patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide ... A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259 ... Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that competes with ATP for the ... Pao W, Miller VA (2005) Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung ...
Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a ... Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that ... Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that ... Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a ...
  • Abstract -Angiotensin II (Ang II) is a vasoactive hormone with critical roles in vascular smooth muscle cell growth, an important feature of hypertension and atherosclerosis. (ahajournals.org)
  • Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): a regulator of several pathways. (springer.com)
  • We propose that CIN85 functions as a scaffold molecule that binds to numerous endocytic accessory proteins, thus controlling distinct steps in trafficking of EGF receptors along the endocytic and recycling pathways. (diva-portal.org)
  • These findings emphasize the importance of ROS in specific Ang II-stimulated growth-related signaling pathways and suggest that redox-sensitive EGF-R transactivation may be a potential target for antioxidant therapy in vascular disease. (ahajournals.org)
  • 13 Although α 1 -AR stimulation has been shown to activate ERK1/2 (also denoted p42/p44 MAPK) in cultured SMCs, 4,14,15 no studies have determined which MAPK pathways are required for α 1 -AR-induced growth in the intact artery. (ahajournals.org)
  • The proximal signals linking GPCRs to downstream MAPK pathways and cell growth are less well defined than those for RTKs. (ahajournals.org)
  • Brogden NK, Mehalick L, Fischer CL, Wertz PW, Brogden KA (2012) The emerging role of peptides and lipids as antimicrobial epidermal barriers and modulators of local inflammation. (springer.com)
  • CIN85 src homology 3 domains specifically bind to a proline-arginine (PxxxPR) motif in Cbl, and this association seems to be important for EGF receptor endocytosis. (diva-portal.org)
  • These results suggest that the loss of EGF receptors in ovarian hormone dependent mammary tumors does not occur gradually during carcinogenesis but appears to be a characteristic of hormone dependent mammary tumor cells. (spandidos-publications.com)
  • The ErbB family members are cell surface receptors that are expressed in most tissues throughout the body and form both homo- and heterodimers to generate signals. (springer.com)
  • These cell surface receptors play an important role in the flow of information from the outside of a cell to the inside. (activemotif.com)