Overexpression of PKCε sensitizes LNCaP human prostate cancer cells to induction of apoptosis by bryostatin 1

Phorbol 12-myristate 13-acetate (PMA)-induced apoptosis of androgen sensitive LNCaP human prostate cancer cells is a well known phenomenon that involves prolonged translocation of multiple protein kinase C (PKC) isozymes to nonnuclear membranes. We have shown recently that PMA-induced death of C4-2 cells, androgen hypersensitive derivatives of LNCaP cells, requires both PKC delta and a redundant pathway that includes PKCs alpha and epsilon epsilon. In contrast, it has been reported that overexpression of murine PKC epsilon in LNCaP cells renders those cells resistant to PMA-induced death, as well as androgen insensitive. Here we report that inducible or constitutive overexpression of human PKC epsilon does not alter the sensitivity of LNCaP cells to either PMA or androgen, nor does it alter expression of caveolin-1 or phosphorylated Rb, reported effects of overexpression of murine PKC epsilon. Moreover, overexpression of very high amounts of PKC epsilon sensitized LNCaP cells to induction of apoptosis by bryostatin 1, a non tumor-promoting activator and down-regulator of PKC isozymes that blocks PMA-induced apoptosis of parental LNCaP cells, mimicked our previous results with overexpression of PKC alpha in LNCaP cells. Given reports that overexpression of PKC epsilon: is frequent in human prostate tumors, our results may have important implications for a potential prostate cancer therapy. (c) 2005 Wiley-Liss, Inc.