Effect of phorbol ester on growth of tumors induced by Rous sarcoma virus and on pp60src kinase activity in these tumors.

The inoculation of Rous sarcoma virus (RSV) into chickens results in the induction of tumors which usually grow progressively for several weeks and then regress. We have found that the direct injection of phorbol myristate acetate into growing RSV-induced sarcomas resulted in accelerated tumor regression in each of 11 cases studied. We further found that treatment of cultured Rous sarcoma cells with phorbol myristate acetate for 72 h resulted in a 50% diminution in numbers of viable cells, in comparison with controls, and a 60% reduction in DNA synthesis. We also investigated alterations in the pp60src kinase activity of cultured RSV-induced tumor cells after treatment with phorbol myristate acetate and found that pp60src kinase activity was reduced to 65-95% of control levels. This inhibition of pp60src kinase was both time- and concentration-dependent. Western blot analysis, using a tumor-bearing rabbit serum, indicated that the pp60src protein was reduced by 35-65% in treated cells, while Pr76, precursor of the structural RSV-proteins, was diminished by 10-35%. In contrast, nonviral proteins such as actin were not significantly affected.