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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Protein Kinase C
Colon
Carcinogenesis
Catenins
Adenomatous Polyposis Coli
Intestinal Mucosa
Aberrant Crypt Foci
Azoxymethane
Glycogen Synthase Kinase 3
Transgenic Mice
Epithelium
Epithelial Cells
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Overexpression of protein kinase C β(II) induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. / Murray, Nicole R; Davidson, Laurie A.; Chapkin, Robert S.; Gustafson, W. Clay; Schattenberg, Diane G.; Fields, Alan P.

In: Journal of Cell Biology, Vol. 145, No. 4, 17.05.1999, p. 699-711.

Research output: Contribution to journalArticle

Murray, Nicole R ; Davidson, Laurie A. ; Chapkin, Robert S. ; Gustafson, W. Clay ; Schattenberg, Diane G. ; Fields, Alan P. / Overexpression of protein kinase C β(II) induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. In: Journal of Cell Biology. 1999 ; Vol. 145, No. 4. pp. 699-711.
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