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.
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.
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.
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)
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
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.
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
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.
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.
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).
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
The fluid surrounding the OVUM and GRANULOSA CELLS in the Graafian follicle (OVARIAN FOLLICLE). The follicular fluid contains sex steroids, glycoprotein hormones, plasma proteins, mucopolysaccharides, and enzymes.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A sulfathiazole antibacterial agent.
A product of the PLACENTA, and DECIDUA, secreted into the maternal circulation during PREGNANCY. It has been identified as an IGF binding protein (IGFBP)-4 protease that proteolyzes IGFBP-4 and thus increases IGF bioavailability. It is found also in human FIBROBLASTS, ovarian FOLLICULAR FLUID, and GRANULOSA CELLS. The enzyme is a heterotetramer of about 500-kDa.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
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.
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.
Proteins prepared by recombinant DNA technology.
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.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The hormone-responsive glandular layer of ENDOMETRIUM that sloughs off at each menstrual flow (decidua menstrualis) or at the termination of pregnancy. During pregnancy, the thickest part of the decidua forms the maternal portion of the PLACENTA, thus named decidua placentalis. The thin portion of the decidua covering the rest of the embryo is the decidua capsularis.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
Cell surface receptors that bind somatomedins and trigger intracellular changes which influence the behavior of cells. Studies have disclosed two types of receptors for this family of peptide hormones. The type I receptor is homologous to the insulin receptor and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor which is important in trafficking of lysosomal enzymes.
A cell line derived from cultured tumor cells.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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).
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
The rate dynamics in chemical or physical systems.
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.
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
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.
Tumors or cancer of the human BREAST.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
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.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
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.
Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).
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 molecules that are involved in the control of cell growth and differentiation.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
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.
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.
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.
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.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
The sum of the weight of all the atoms in a molecule.
A subclass of tumor necrosis family receptors that lack cell signaling domains. They bind to specific TNF RECEPTOR LIGANDS and are believed to play a modulating role in the TNF signaling pathway. Some of the decoy receptors are products of distinct genes, while others are products of ALTERNATIVE SPLICING of the MRNA for the active receptor.
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.
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.
Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.
Glucose in blood.
Tumors or cancer of the PROSTATE.
A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
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.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
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.
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.
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Insulin formulations that contain substances that retard absorption thus extending the time period of action.
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.
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.
Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.