Differential response to retinoic acid of Syrian hamster embryo fibroblasts expressing v-src or v-Ha-ras oncogenes.
It has been shown that treatment of many but not all tumor cell lines with retinoids affects cell proliferation and expression of the transformed phenotype. To determine whether the response of the tumor cell to retinoids is influenced by specific oncogenes activated in the cell, we studied the action of these agents in the immortal, nontumorigenic Syrian hamster embryo cell lines DES-4 and 10W transfected with either v-Ha-ras or v-src oncogenes. In this paper we show that in transformed DES-4 cells expressing v-src, retinoic acid inhibited anchorage-independent growth, reduced saturation density, and inhibited the induction of ornithine decarboxylase by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. In contrast, retinoic acid enhances the expression of the transformed phenotype in DES-4-derived cells that express v-Ha-ras. In these cells retinoic acid increases the number and the average size of colonies formed in soft agar. Moreover, retinoic acid enhances ornithine decarboxylase activity and acts in a synergistic fashion with 12-O-tetradecanoylphorbol-13-acetate. These results indicate that oncogenes activated in cells can indeed influence the response of cells to retinoids. Retinoic acid does not appear to alter the levels of pp60src or p21ras proteins in these cells, suggesting that retinoic acid does not affect the synthesis of these oncogene products. Furthermore, retinoic acid does not affect the protein kinase activity of pp60src. Transformed cell lines derived from 10W cells responded differently, indicating that the presence of a specific oncogene is not the only factor determining the response to retinoids. Possible mechanisms by which retinoic acid may interfere with the expression of the oncogene products are discussed.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects; D005796:Genes; D005814:Genes, Viral; D006168:Guinea Pigs; D007700:Kinetics; D015689:Oncogene Protein p21(ras); D015688:Oncogene Protein pp60(v-src); D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D009955:Ornithine Decarboxylase / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D009856:Oncogene Proteins, Viral; D012191:Retroviridae Proteins; D014212:Tretinoin; D015688:Oncogene Protein pp60(v-src); D015689:Oncogene Protein p21(ras); D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate