Specific growth response of ras-transformed embryo fibroblasts to tumour promoters.
Chemical carcinogenesis is a process involving multiple steps, as shown in several in vivo experimental systems. Two early steps have been well characterized: initiation, achieved by a single, subthreshold dose of a carcinogen, and promotion, induced by repetitive treatments with a non-carcinogenic tumour promoter. At the cellular level, establishment of the transformed phenotype is also a multi-step process and activation of several, independent genes appears to be required. Here we show that, like initiated cells, primary rat embryo fibroblasts (REFs) containing a ras but not a myc oncogene, are strongly and specifically stimulated to grow by tumour promoters. In the presence of these promoters, ras-containing REFs acquire the ability to overgrow normal cells in the monolayer and to form foci with 100% efficiency. Similar to the in vivo situation, promoter effects can be blocked by the concomitant application of retinoic acid.
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects; D009857:Oncogenes; D010704:Phorbols / Q000633:toxicity*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014162:Transfection
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate