Two classes of cAMP analogs synergistically inhibit p21 ras protein synthesis and phenotypic transformation of NIH/3T3 cells transfected with Ha-MuSV DNA.

Factors that control cellular proliferation might do so by regulating quantitative expression of viral or cellular oncogenes. Since the growth regulatory effect of cAMP is well-known, the effect of cAMP on ras gene expression was examined on Ha-MuSV-transformed 13-3B-4 cells (NIH-3T3) grown in chemically defined serum-free medium. Treatment of cells with two classes of cAMP analogs which are selective for the two different cAMP-binding sites of type II protein kinase, in combination, synergistically inhibited both p21 ras protein synthesis and phenotypic transformation. The inhibition was also demonstrated with these analogs singly but at higher concentrations. The decrease in p21 synthesis was inversely correlated with an increase in the RII cAMP receptor protein, the regulatory subunit of type II protein kinase. These results suggest a role for cAMP and its receptor protein in the regulation of v-rasH oncogene expression.