[Possible modes of action of growth factors and tumor promoters in the activation of the c-myc gene in Swiss 3T3 fibroblasts].
It has been suggested that the c-myc gene may play an important role in the regulation of cell proliferation. We have investigated the transmembrane signaling mechanisms of various growth factors and tumor promoters in Swiss 3T3 fibroblasts and have examined the causal relationship between these mechanisms and c-myc gene activation. Platelet-derived growth factor and FGF (fibroblast growth factor) induced the activation of diglyceride-protein kinase C and Ca2+ systems through phosphoinositide turnover, resulting in the activation of the c-myc gene. Epidermal growth factor did not activate these two systems but stimulated gene activation. Prostaglandin E1 elicited Ca2+ mobilization and cyclic AMP generation followed by c-myc gene activation. In contrast to these growth factors, tumor-promoting phorbol esters induced the direct activation of protein kinase C which led to c-myc gene expression. Bile acids, which are known to be colon tumor promoters, were inactive by themselves but enhanced FGF-induced diglyceride formation and thereby potentiated protein kinase C activation. It has not yet been examined whether bile acids potentiate FGF-induced activation of the c-myc gene. The growth factors described above and the phorbol esters stimulated DNA synthesis in the presence of insulin, whereas the bile acids potentiated FGF-induced DNA synthesis. These results strongly suggest that three messenger systems, diglyceride, Ca2+ and cyclic AMP, may be involved in c-myc gene activation which may be implicated in DNA synthesis in Swiss 3T3 cells.
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011458:Prostaglandins E / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D015533:Transcriptional Activation
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors; D004247:DNA; D000242:Cyclic AMP; D011493:Protein Kinase C