Overexpression of Protein Kinase C β_II Induces Colonic Hyperproliferation and Increased Sensitivity to Colon Carcinogenesis

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.