Retinoic acid regulates selectively the expression of immediate early response genes in PC12 cells

Nerve growth factor (NGF) induces neuronal differentiation and growth arrest in PC12 cells. One of the initial effects of NGF in these cells is the induction of the expression of immediate early genes (IEGs). In this study we have analyzed the influence of retinoic acid (RA), which exerts important effects on PC12 cell proliferation and function, on the expression of IEGs. Incubation with RA did not alter NGFI-A mRNA levels, but significantly reduced the NGFI-B and c-fos response to NGF and serum. The response to NGF was maximal in the presence of cycloheximide, and RA also reduced the superinduction of NGFI-B and c-fos mRNA levels. Sequences contained within the 5' flanking region of the c-fos gene confer responsiveness to NGF and mediate the inhibitory effect of RA. The differential regulation by RA suggests that NGF induces expression of the three IEGs by different mechanisms.