Overexpression of protein kinase C βII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis

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