Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells.

The nerve growth factor (NGF)-mediated increase in c-fos gene expression in the rat pheochromocytoma PC12 cell line has been investigated. NGF treatment of PC12 cells results in an increased level of c-fos mRNA within 15 min. An approximately 100-fold increase in the level of c-fos mRNA occurs 30-45 min after exposure to NGF and the c-fos mRNA concentration returns to its basal level 2 hr after NGF treatment. Thus, the half-life of this RNA transcript is extremely short. In the presence of cycloheximide, the c-fos gene is superinduced and the increased level of c-fos mRNA persists for at least 24 hr. The induction of c-fos gene expression was further studied by utilizing a monoclonal antibody (mAb-192) that is directed against the NGF receptor but does not compete with NGF for binding to the receptor. Treatment of the cells with mAb-192 inhibits the NGF-stimulated elevation of c-fos mRNA, suggesting that the antibody may interfere with the receptor's ability to generate the signal required to stimulate the transcription of this gene. NGF is not the only agent capable of inducing c-fos gene expression in these cells; epidermal growth factor, the tumor promoter phorbol 12-myristate 13-acetate, and the calcium ionophore A23187, agents that induce the c-fos gene in other cell lines, are also effective in PC12 cells. The mRNA for the nuclear protein fos is rapidly induced by NGF and other agents to which PC12 cells respond. This supports the hypothesis that the fos gene product may play a role in signal transduction.