J. Cell Biol., Volume 145, Number 4, May 17, 1999 699-711

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

Nicole R. Murray,^* Laurie A. Davidson, Robert S. Chapkin, W. Clay Gustafson,^* Diane G. Schattenberg,^* and Alan P. Fields^*§

^* Sealy Center for Oncology and Hematology,  Department of Human Biological Chemistry & Genetics, and ^§ Department of Pharmacology, University of Texas Medical Branch, Galveston, Texas 77555-1048; and  Faculty of Nutrition, Molecular and Cell Biology Section, Texas A&M University, College Station, Texas 77843-2471

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

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