Differential induction of c-fos and c-myc by cyclic AMP in Swiss 3T3 cells: significance for the mitogenic response.

Overview

Quiescent Swiss 3T3 cells can be stimulated to reinitiate DNA synthesis through specific intracellular signalling pathways which include an increase in cyclic AMP levels and the activation of protein kinase C. In the present study we have compared the effect of these two pathways on the expression of c-fos and c-myc in Swiss 3T3 cells. In cells treated with the cyclic AMP-elevating agents forskolin or prostaglandin E1 or with the permeable cyclic AMP analogue, 8-bromo cyclic AMP, the levels of c-fos messenger RNA were 5 to 10% of those induced by bombesin, which activates protein kinase C. In contrast, a dramatic and comparable increase in the expression of c-myc messenger RNA was observed when cells were treated either with the cyclic AMP-increasing agents or with bombesin. Thus an increase in cyclic AMP leads to the differential induction of c-fos and c-myc messenger RNA in Swiss 3T3 cells. Significantly, we obtained comparable results when cells were treated with a mitogenic combination of cyclic AMP and insulin. Furthermore, these findings have been confirmed at the protein level. We concluded that the large induction of c-fos can be dissociated from cyclic AMP-mediated mitogenesis in Swiss 3T3 cells.