Overexpression of protein kinase C β(II) induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis

Abstract

Protein kinase C β(II) (PKC β(II)) has been implicated in proliferation of the intestinal epithelium. To investigate PKC β(II) function in vivo, we generated transgenic mice that overexpress PKC β(II) in the intestinal epithelium. Transgenic PKC β(II) mice exhibit hyperproliferation of the colonic epithelium and an increased susceptibility to azoxymethane-induced aberrant crypt foci, preneoplastic lesions in the colon. Furthermore, transgenic PKC β(II) mice exhibit elevated colonic β- catenin levels and decreased glycogen synthase kinase 3β activity, indicating that PKC β(II) stimulates the Wnt/adenomatous polyposis coli (APC)/β-catenin proliferative signaling pathway in vivo. These data demonstrate a direct role for PKC β(II) in colonic epithelial cell proliferation and colon carcinogenesis, possibly through activation of the APC/β-catenin signaling pathway.