Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines.
Alterations in proto-oncogene expression after stimulation of rat pheochromocytoma (PC12) cells by nerve growth factor (NGF) have been investigated. A specific stimulation of c-fos messenger RNA and protein was detected 30 minutes after treatment. This induction was enhanced more than 100-fold in the presence of peripherally active benzodiazepines. The effect was specific as very little change was observed in the levels of c-rasHa, c-rasKi, c-myc, and N-myc messenger RNA's. Under the conditions used here, NGF treatment ultimately results in neurite outgrowth, with a reduction or cessation of cell division. Thus, stimulation of the c-fos gene in this system appeared to be associated with differentiation and not with cellular proliferation. The effect of benzodiazepines was stereospecific and represents a novel action of these compounds at the level of gene expression.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009857:Oncogenes; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D001569:Benzodiazepines