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

60 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Protein Kinase C
Colon
Carcinogenesis
Fatty Acids
Colonic Neoplasms
Transgenic Mice
Rodentia
Epithelium
Epithelial Cells

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Protein kinase C βII and TGFβRII in ω-3 fatty acid-mediated inhibition of colon carcinogenesis. / Murray, Nicole R; Weems, Capella; Chen, Lu; Leon, Jessica; Wangsheng, W.; Davidson, Laurie A.; Jamieson, Lee; Chapkin, Robert S.; Thompson, E Aubrey; Fields, Alan P.

In: Journal of Cell Biology, Vol. 157, No. 6, 10.06.2002, p. 915-920.

Research output: Contribution to journalArticle

Murray, Nicole R ; Weems, Capella ; Chen, Lu ; Leon, Jessica ; Wangsheng, W. ; Davidson, Laurie A. ; Jamieson, Lee ; Chapkin, Robert S. ; Thompson, E Aubrey ; Fields, Alan P. / Protein kinase C βII and TGFβRII in ω-3 fatty acid-mediated inhibition of colon carcinogenesis. In: Journal of Cell Biology. 2002 ; Vol. 157, No. 6. pp. 915-920.
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