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.
Randazzo
P A
PA
Department of Pathology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Jarett
L
L
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