Oncogene transcription in normal human IMR-90 fibroblasts: induction by serum and tetradecanoyl phorbol acetate.
We report studies of oncogene transcription induced by the addition of serum to quiescent cultures of human IMR-90 fibroblasts. Oncogene messenger RNAs for c-myc, c-erbB and c-ras were increased in a specific temporal sequence after the addition of serum. Compounds that are proposed to exert their actions by the stimulation of cell growth were tested for their effect on oncogene transcription in IMR-90 fibroblasts. The tumor promoter tetradecanoyl phorbol acetate (TPA) was found to selectively induce the transcription of c-myc without observable effect on the transcription of the other oncogenes studied, and without inducing cell division. The inactive analog, phorbol didecanoate (PDD), and two complete carcinogens dimethylbenzanthracene (DMBA) and 4-nitro quinoline-1-oxide (4NQO) were without effect on the transcription of the genes studied. These results suggest that the complete ordered sequence of gene transcription is necessary to achieve the physiologic response of cell division, and that classical promoters and complete carcinogens achieve their effects through different pathways.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D001769:Blood; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D009857:Oncogenes; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D010703:Phorbol Esters; D012333:RNA, Messenger; C008876:phorbol-12,13-didecanoate; D015112:4-Nitroquinoline-1-oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate