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, Alan P. Fields

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)699-711
Number of pages13
JournalJournal of Cell Biology
Volume145
Issue number4
DOIs
StatePublished - May 17 1999

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Keywords

  • Colon carcinogenesis
  • Proliferation
  • Protein kinase C
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology

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