Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors.
The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity.
Department of Pathology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
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Randazzo
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Jarett
D000818:Animals; D002455:Cell Division / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D006133:Growth Substances; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D014316:Tritium; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D011972:Receptor, Insulin; D013936:Thymidine