Transgenic overexpression of PKCε in the mouse prostate induces preneoplastic lesions

It is well established that protein kinase C (PKC) isozymes play distinctive roles in mitogenic and survival signaling as well as in cancer progression. PKC epsilon, the product of the PRKCE gene, is upregulated in various types of cancers including prostate, lung and breast cancer. To address a potential role for PKCs in prostate cancer progression we generated three mouse transgenic lines expressing PKC alpha, PKC delta or PKC epsilon in the prostate epithelium under the control of the rat probasin (PB) promoter. Whereas PB-PKC alpha and PB-PKC delta mice did not show any evident phenotype, PB-PKC epsilon mice developed prostate hyperplasia as well as prostate intraepithelial neoplasia (PIN) that displayed enhanced phospho-Akt, phospho-S6 and phospho-Stat3 levels, as well as enhanced resistance to apoptotic stimuli. PKC epsilon overexpression was insufficient to drive neoplastic changes in the mouse prostate. Notably, overexpression of PKC epsilon by adenoviral means in normal immortalized RWPE-1 prostate cells confers a growth advantage and hyperactivation of Erk and Akt. Our results argue for a causal link between PKC epsilon overexpression and prostate cancer development.