Dissociation of c-fos induction from protein kinase C-independent mitogenesis in Swiss 3T3 cells.

Bombesin is a potent mitogen for Swiss 3T3 cells and can act synergistically with insulin to stimulate DNA synthesis through protein kinase C-dependent and -independent pathways. One of the earliest nuclear responses of quiescent cells treated with a combination of bombesin and insulin is a dramatic increase in c-fos expression. Here we report that the selective down-regulation of protein kinase C (PKC) caused a 90-97% decrease in the induction of c-fos mRNA and fos protein expression but did not affect the mitogenic response to bombesin and insulin. These observations were confirmed in detailed dose-response and time-course experiments. We conclude that the large induction of c-fos is not an obligatory event for mitogenesis in Swiss 3T3 cells.