The effects of p21N-ras expression in NIH-3T3 cells upon cyclic AMP metabolism.

The effects of overexpression of p21N-ras upon cyclic AMP metabolism have been examined in the inducible T15 cell line. In cells overexpressing the N-ras gene product, beta-adrenergic stimulation of cyclic AMP generation was reduced. The reduction was more pronounced the longer the ras gene was expressed and in chronically transformed cells a reduction in forskolin-stimulated cyclic AMP generation was also observed. The transformed cells exhibited a reduction in beta-adrenergic binding sites, but no change in the apparent EC50 for agonist induced cyclic AMP generation. Treatment of the cells with dibutyryl cyclic AMP induced a dose-dependent inhibition of proliferation, with the transformed cells being more sensitive than the control cells.