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

Protein kinase C beta(II) (PKC beta(II)) has been implicated in proliferati on of the intestinal epithelium. To investigate PKC beta(II) function in vi vo, we generated transgenic mice that overexpress PKC beta(II) in the intes tinal epithelium. Transgenic PKC beta(II) mice exhibit hyperproliferation o f the colonic epithelium and an increased susceptibility to azoxymethane-in duced 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 ro le for PKC beta(II) in colonic epithelial cell proliferation and colon carc inogenesis, possibly through activation of the APC/beta-catenin signaling p athway.