Possible involvement of protein kinase C and calcium ion in growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts

• Published in: The Journal of biological chemistry 1986-01, Vol.261 (3), p.1187-1192
• Main Authors: Kaibuchi, K, Tsuda, T, Kikuchi, A, Tanimoto, T, Yamashita, T, Takai, Y
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcimycin - pharmacology; Calcium - metabolism; Cell Line; Diglycerides - pharmacology; Enzyme Activation; Ethers - pharmacology; Fibroblast Growth Factors - pharmacology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - drug effects; Ionomycin; Mice; Molecular and cellular biology; Molecular genetics; Oncogenes; Phorbol 12,13-Dibutyrate; Phorbol Esters - pharmacology; Platelet-Derived Growth Factor - pharmacology; Protein Kinase C - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)36074-X

The addition of platelet-derived growth factor and fibroblast growth factor to quiescent cultures of Swiss 3T3 fibroblasts rapidly induced protein kinase C activation and Ca2+ mobilization and afterwards markedly increased c-myc mRNA levels. 1-Oleoyl-2-acetylglycerol, a membrane-permeable synthetic diacylglycerol, and 12-O-tetradecanoylphorbol 13-acetate, a tumor-promoting phorbol ester, stimulated protein kinase C activation without Ca2+ mobilization. Inversely, Ca2+ ionophores, A23187 and ionomycin, elicited Ca2+ mobilization without protein kinase C activation. Both protein kinase C-activating and Ca2+-mobilizing agents were able to increase c-myc mRNA levels in an additive manner. Prolonged treatment of the cells with phorbol 12,13-dibutyrate, another protein kinase C-activating phorbol ester, led to the down-regulation and complete disappearance of protein kinase C. In these cells, 1-oleoyl-2-acetylglycerol and 12-O-tetradecanoylphorbol 13-acetate did not increase c-myc mRNA levels, but platelet-derived growth factor, fibroblast growth factor, and the Ca2+ ionophores, all of which still induced Ca2+ mobilization, stimulated the increase of c-myc mRNA levels. These results strongly suggest that both protein kinase C and Ca2+ may be involved in platelet-derived growth factor- as well as fibroblast growth factor-induced expression of the c-myc oncogene in Swiss 3T3 cells.