The ras oncogene inhibits growth factor inducibility of early response genes, and promotes selectively expression of NGFI-A in a PC12 cell line.

Expression of oncogenic Ras in UR61 cells (a PC12 subclone) results in neuronal differentiation. We have observed that the oncoprotein selectively increased the levels of NGFI-A transcripts, but was unable to induce NGFI-B or c-fos transcripts. In contrast, nerve growth factor (NGF) elicited a strong induction of the three immediate early genes (IEGs). Thus, activation of Ras alone is sufficient for the induction of NGFI-A by NGF, whereas an additional pathway(s), besides Ras, is required for the stimulation of NGFI-B and c-fos gene expression. These results show that the acquisition of a neuronal phenotype does not correlate with induction of IEG expression. Additionally, Ras markedly reduces the response of the three genes to NGF and to other growth factors. This attenuation could reflect a negative regulatory mechanism acting on signalling pathways normally stimulated by growth factor receptors.