Cyclic AMP inhibits c-Ha-ras protooncogene expression and DNA synthesis in rat aortic smooth muscle cells

Fetal bovine serum (10%) markedly increased ras transcript levels in growth-arrested (G0-synchronized) smooth muscle cells by 8 h. This elevation was maintained for up to 18 h and returned to pre-stimulation levels within 24 h. Challenge of quiescent cells with serum in the presence of dibutyryl cyclic AMP (1-100 microM, a growth inhibitor for smooth muscle cells, attenuated serum-induced elevation of c-Ha-ras in a dose dependent fashion and prevented progression of the cells into S phase. These results demonstrate that expression of c-Ha-ras in rat aortic smooth muscle cells is cell-cycle dependent and that cAMP prevents the induction of this protooncogene by serum.