Control of endogenous cell regulators by the second-stage tumor promoter phorbol-12-retinoate 13-acetate

The phorbol esters phorbol 12-retinoate 13-acetate (RPA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) were used to investigate the role of tumor promoters in the control of hormone response in normal and leukemic myeloid cells. RPA and TPA inhibited the binding of [20-3H]phorbol 12,13-dibutyrate to the leukemic cells in a competitive manner with 50% inhibition values of 5.2 +/- 1.3 and 1.1 +/- 0.6 nM, respectively. RPA, like TPA, enhanced (1) prostaglandin E1-induced cyclic AMP synthesis, (2) the differentiation of leukemic cells induced by the normal myeloid differentiation-inducing protein, and (3) the formation of normal myeloid cells colonies induced by the normal myeloid growth-inducing protein. Both compounds can thus control endogenous cell regulators. Since RPA functions in the second stage of tumor promotion in mouse skin, it is suggested that the control of such endogenous regulators may involve biochemical pathways similar to those that are activated in the second stage of tumor promotion.