Protein Kinase C and Prostate Carcinogenesis: Targeting the Cell Cycle and Apoptotic Mechanisms

M.   Veronica   Gavrielides; Anita   F.   Frijhoff; Claudio   J.   Conti; Marcelo   G.   Kazanietz

Abstract

A series of both genetic and epigenetic factors have been implicated in the genesis and progression of prostate cancer. Recent evidence revealed that protein kinase C (PKC) isozymes play a crucial role in the control of cell proliferation and apoptosis in prostate cancer models, as well as in the transition from an androgen-dependent to an androgen-independent status. Indeed, PKCa and PKCd promote apoptosis in androgen-dependent prostate cancer cells. Due to the relevance of PKC isozymes in the control of cell cycle, both in G1/S and G2 / M, the elucidation of such complex intracellular networks using cellular and animal models has become of outmost importance. In this review, we present the current knowledge on the regulation of apoptosis and tumorigenicity by PKC isozymes and the functional roles of cell cycle regulators in prostate carcinogenesis. The development of animal models where overexpression of discrete PKCs or cell cycle regulators is targeted to the prostate will greatly contribute to the understanding of the molecular basis of the disease, and more importantly, it will have profound implications for the development of novel strategies for prostate cancer therapy.

Keywords: protein kinase c, pkc isozymes, prostate carcinogenesis, cell cycle, apoptosis, animal models, phorbol esters, androgen