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


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Abstract

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 PKCδ and a redundant pathway that includes PKCs α and ε. In contrast, it has been reported that overexpression of murine PKCε 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 PKCε 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 PKCε. Moreover, overexpression of very high amounts of PKCε 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 PKCα in LNCaP cells. Given reports that overexpression of PKCε is frequent in human prostate tumors, our results may have important implications for a potential prostate cancer therapy.

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