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PMID: 12058013 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Protein kinase C betaII and TGFbetaRII in omega-3 fatty acid-mediated inhibition of colon carcinogenesis.

The Journal of cell biology ·Vol. 157 ·No. 6 ·2002-06-10 ·Pages 915-20

Murray NR, Weems C, Chen L, Leon J, Yu W, Davidson LA, Jamieson L, Chapkin RS, Thompson EA, Fields AP

Abstract

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

MeSH Terms
Animals Cell Division Colonic Neoplasms/enzymology,etiology,pathology Fatty Acids, Omega-3/metabolism Intestinal Mucosa/cytology Isoenzymes/genetics,metabolism,physiology Mice Mice, Transgenic Protein Kinase C/genetics,metabolism,physiology Protein Kinase C beta Rats Rats, Sprague-Dawley Receptors, Transforming Growth Factor beta/genetics,metabolism,physiology Signal Transduction
Chemicals
Fatty Acids, Omega-3 Isoenzymes Receptors, Transforming Growth Factor beta Protein Kinase C Protein Kinase C beta
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Murray Nicole R
Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1048, USA.
Weems Capella
Chen Lu
Leon Jessica
Yu Wangsheng
Davidson Laurie A
Jamieson Lee
Chapkin Robert S
Thompson E Aubrey
Fields Alan P
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200201127
Published
2002-06-10
Epub
2002-00-10
Pages
915-20
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2174056
Subset
IM
Grants
NCI NIH HHS · R01 CA081436 · United States
NCI NIH HHS · CA81436 · United States
NCI NIH HHS · CA24347 · United States
NCI NIH HHS · R01 CA059034 · United States
NCI NIH HHS · CA59034 · United States
NCI NIH HHS · R01 CA024347 · United States
External Links
PubMed source DOI: 10.1083/jcb.200201127 PMC Full Text View journal details
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