title: Inhibition of mitogen-induced c-fos expression in melanoma cells by retinoic acid involves the serum response element.
abstract: To investigate the mechanism(s) by which all-transretinoic acid (RA) inhibits cell growth, we studied its effect on the expression of c-fos and c-jun in B16 melanoma cells. RA differentially inhibited proto-oncogene induction by mitogens, such as phorbol 12-myristate 13-acetate and serum. Suppression of c-fos was achieved with doses of RA as low as 10(-10) M and required pretreatment of cells with RA for a minimum of 2 h. In contrast, inhibition of c-jun required pretreatment for greater than 16 h with at least 10(-8) M RA and coincided with the observed decrease in cell growth. RA blocked c-fos induction by inhibiting transcription. This inhibition of transcription occurs through the serum response element (SRE), since the SRE alone was sufficient to confer down-regulation by RA to a minimal c-fos promoter construct. Thus, the SRE plays a critical role in the suppression of c-fos transcription by RA.
authors.affiliation: Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: K J
authors.initials: KJ
authors.lastname: Busam
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun / Q000187:drug effects; D008546:Melanoma, Experimental; D051379:Mice; D008934:Mitogens / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins; D010957:Plasmids; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D026362:Serum Response Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D008934:Mitogens; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate