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© The Rockefeller University Press, 0021-9525/1999//699 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 699-711

Overexpression of Protein Kinase C β_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 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.

Key Words: protein kinase C • colon carcinogenesis • signal transduction • proliferation • transgenic mice

Abbreviations used in this paper: ACF, aberrant crypt foci; AOM, azoxymethane; APC, adenomatous polyposis coli; DAG, diacylglycerol; DBA, dolichos biflorus agglutinin; FABP, fatty acid binding protein; GSK-3β, glycogen synthase kinase 3β; PAS, periodic acid Schiff; PKC, protein kinase C; PKC β_II, protein kinase C β_II isozyme; PNA, peanut agglutinin; RT-PCR, reverse transcriptase PCR; TUNEL, TdT-mediated dUTP-biotin nick end labeling; UEAI, Ulex europaeus-I.

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