Nerve growth factor-induced neuronal differentiation of PC12 pheochromocytoma cells: Lack of inhibition by a tumor promoter

Abstract

Reports of inhibition of vitro neuronal and non-neuronal differentiation by tumor promote prompted the study of effects of phorbol myristate acetate (PMA), a potent tumor promoter, on PC12 rat pheochromocytoma cells. PC12 cells are a well characterized in vitro cell line which undergoes initiation of neurite outggrowth transcription-requiring cellular response to nerve growth factor (NGF). Cells which have been incubated in the presence of NGF for a week also acquire the capacity for rapid, transcription-independent regeneration of neurites. This capacity is known as ‘NGF-priming’. We show that PMA does not inhibit initiation, regeneration, or NGF-priming of PC12 cells. This contrasts with previously reported inhibitory effects of PMA on neurite outgrowth in other cell types. However, morphologic l changes induced by PMA in PC12 cells are consistent with reduced neurite-substrate adhesion. PMA appears to shift the dose-response curve of NGF so that low doses of NGF are more effective in initiating neurite outgrowth.