Protein kinase C βII and TGFβRII in ω-3 fatty acid-mediated inhibition of colon carcinogenesis

Nicole R. Murray, Capella Weems, Lu Chen, Jessica Leon, W. Wangsheng, Laurie A. Davidson, Lee Jamieson, Robert S. Chapkin, E. Aubrey Thompson, Alan P. Fields

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Increasing evidence demonstrates that protein kinase C βII (PKCβII) promotes colon carcinogenesis. We previously reported that colonic PKCβII is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCβII in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCβII represses transforming growth factor β receptor type II (TGFβRII) expression and reduces sensitivity to TGF-β-mediated growth inhibition in intestinal epithelial cells. Transgenic PKCβII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFβRII expression. Chemopreventive dietary ω-3 fatty acids inhibit colonic PKCβII activity in vivo and block PKCβII-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFβII expression in the colonic epithelium of transgenic PKCβII mice. These data indicate that dietary ω-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCβII signaling and restoration of TGF-β responsiveness.

Original languageEnglish (US)
Pages (from-to)915-920
Number of pages6
JournalJournal of Cell Biology
Volume157
Issue number6
DOIs
StatePublished - Jun 10 2002

Keywords

  • Colon carcinogenesis
  • Hyperproliferation
  • Protein kinase C
  • Transforming growth factor β
  • ω-3 fatty acids

ASJC Scopus subject areas

  • Cell Biology

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