Biochemical Mechanisms of Action of the Phorbol Ester Class of Tumor Promoters

Abstract

The discovery by Driedger and Blumberg1 that the phorbol esters functioned through specific receptors, followed by the finding of Castagna et al.2 that the tumor-promoting phorbol esters activated the Ca2+— and phospholipid-dependent protein kinase (protein kinase C), suggesting its identity with the phorbol ester receptor, has had major impact on the understanding of the molecular mechanisms of tumor promotion. Following the initial convergence of these two previously independent research areas, phorbol ester tumor promotion and protein kinase C, a host of related fields such as signal transduction, phosphatidylinositol turnover, growth factors, and oncogenes have also been found to involve the phorbol ester receptor significantly. Hundreds of publications appearing in the literature yearly demonstrate the emphasis on the interactions among these systems.