Canine tracheal epithelial cells express the type 1 insulin-like growth factor receptor and proliferate in response to insulin-like growth factor I. 1990

G Z Retsch-Bogart, and A D Stiles, and B M Moats-Staats, and M R Van Scott, and R C Boucher, and A J D'Ercole
Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220.

Disaggregated airway epithelial cells replicate in serum-free media containing supraphysiologic concentrations of insulin. To examine the hypothesis that the type 1 insulin-like growth factor (IGF) receptor mediates the mitogenic action of insulin on these cells, we studied the mitogenic effects of IGF-I and insulin, and the expression of type 1 IGF receptors in primary cultures of adult canine tracheal epithelial cells. Isolated tracheal epithelial cells were grown in varying concentrations of IGF-I or insulin in Ham's F12 medium supplemented with transferrin, cholera toxin, and endothelial cell growth supplement. Both IGF-I and insulin increased DNA synthesis (measured as [3H]thymidine incorporation into DNA) and cell number in a concentration-dependent fashion, but IGF-I was at least 20 to 60 times more potent than insulin in its mitogenic effects. No additive or synergistic effect was observed with the simultaneous addition of IGF-I and insulin in maximally effective doses. A monoclonal antibody directed against the type 1 IGF receptor (alpha IR3) blocked the mitogenic activity of both IGF-I and insulin. Affinity labeling of type 1 IGF receptors by covalent cross-linking with disuccinimidyl suberate demonstrated the tracheal epithelial cell IGF-I binding moiety to have a relative molecular weight of 130,000 D. Binding of [125I]IGF-I to this protein was inhibited by low concentrations of IGF-I, relative to insulin, and by alpha IR3. An 11-kb transcript characteristic of mRNA for the type 1 IGF receptor was recognized in poly(A+) RNA derived from cultured canine tracheal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007334 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. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008934 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) Mitogen,Phytomitogen,Phytomitogens
D011956 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. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 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. Cultured Cells,Cell, Cultured,Cultured Cell
D004247 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). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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