The potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, produced a 2- to 3-fold increase in the activity of both the low- and high-affinity forms of cyclic adenosine 3′:5′-monophosphate phosphodiesterase activity 13 hr after application to mouse skin. The magnitude of the enzyme induction correlated with the tumor-promoting activity of several doses of 12-O-tetradecanoylphorbol-13-acetate and of other phorbol esters. The induction of the low-affinity phosphodiesterase could be blocked by prior i.p. injection of the microtubule poisons, colchicine and vinblastine. The low-affinity cyclic adenosine 3′:5′-monophosphate phosphodiesterase activity of the epidermal component of mouse skin papillomas produced by two-stage tumorigenesis was 3 times that of the surrounding uninvolved epidermis.
The work was supported by NIH Grants CA 07175 and CA 22484.