Prostaglandin E-mediated Mitogenic Stimulation of Mouse Epidermis in Vivo by Divalent Cation Ionophore A 23187 and by Tumor Promoter 12-O-Tetradecanoylphorbol-13-Acetate¹

When applied to mouse skin in vivo, both the strong tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 nmol) and the divalent cation ionophore A 23187 (200 nmol) caused the same responses, i.e., skin inflammation and prostaglandin E₂-mediated epidermal hyperplasia. In both cases, these events were accompanied by certain biochemical reactions in the epidermis such as an increase in the biosynthesis of and sensitivity to prostaglandin E₂, increases in ornithine decarboxylase and phosphodiesterase activities, and refractoriness of cyclic adenosine 3′:5′-monophosphate production to β-adrenergic stimulation. In contrast to A 23187, TPA did not induce degranulation of mast cells; whereas, in contrast with TPA, A 23187 did not show tumor-promoting activity. These results indicate that the observed biological effects of TPA are no indication of tumor-promoting ability and that, on the other hand, the mitogenic effects of A 23187 are possibly not due to its properties as a calcium ionophore.