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 g rowth-arrested (G0-synchronized) smooth muscle cells by 8 h. This elev ation was maintained for up to 18 h and returned to pre-stimulation le vels within 24 h. Challenge of quiescent cells with serum in the prese nce of dibutyryl cyclic AMP (1-100 muM), a growth inhibitor for smooth muscle cells, attenuated serum-induced elevation of c-Ha-ras in a dos e dependent fashion and prevented progression of the cells into S phas e. These results demonstrate that expression of c-Ha-ras in rat aortic smooth muscle cells is cell-cycle dependent and that cAMP prevents th e induction of this protooncogene by serum.