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.