Protein kinase C β11 and TGFβRII in ω-3 fatty acid-mediated inhibition of colon carcinogenesis

Increasing evidence demonstrates that protein kinase C beta11 (PKCbeta11) promotes colon carcinogenesis. We previously reported that colonic PKCbeta11 is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCbeta11 in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCbeta11 represses transforming growth factor beta receptor type II (TGFbetaR11) expression and reduces sensitivity toTGF-beta-mediated growth inhibition in intestinal epithelial cells. Transgenic PKCbeta11 mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFbetaR11 expression. Chemopreventive dietary w-3 fatty acids inhibit colonic PKCbetaII activity in vivo and block PKCbeta11-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFbetaR11 expression in the colonic epithelium of transgenic PKCbeta11 mice. These data indicate that dietary w-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCbeta11 signaling and restoration of TGF-beta responsiveness.