Abstract 276: Docosahexaenoic acid alters the spatio-temporal segregation and activation of EGF receptor Conference Paper uri icon

abstract

  • Abstract We have previously demonstrated that dietary docosahexaenoic acid (DHA, 22:6n-3), a component of fish oil, profoundly alters the biochemical make up of colonocyte lipid rafts/caveolae microdomains. Since epidermal growth factor receptor (EGFR, ErbB1) is considered a major target for treatment of colorectal cancer and its activation can be regulated by manipulating the lipid composition of the membrane, we further elucidated the effects of DHA with respect to the EGFR signaling axis. Immortalized mouse colonocytes (YAMC cells) were treated with fatty acids (50 M) for 72 h and stimulated in the presence or absence of EGF (0-50 ng/mL) for 0-10 min and receptor stimulation was assessed by determining levels of phosphotyrosine-EGFR. Downstream signaling was evaluated by measuring Akt, ERK 1/2, and Stat3 phosphorylation. EGFR phosphorylation was increased <2-fold (p>0.05) in DHA treated cells compared to control. Erk 1/2 activation was significantly increased <4-fold, while Stat 3 activation was decreased by 2-fold (p>0.05). No change in activation of Akt was observed. In addition, chronically inflamed (DSS treated) and carcinogen (AOM) injected C57BL/6 mice were maintained on diets DHA (fish oil) for 18 wks. Protein from scraped colonic mucosa was analyzed for EGFR phosphorylation and downstream signaling. DHA-fed animals displayed <2-fold (p>0.05) increase in EGFR phosphorylation compared to corn oil fed animals. Total Erk 1/2 and activated Erk 1/2 were significantly increased in DHA-fed animals. Stat3 phosphorylation was decreased by 3-fold (p>0.05). Akt activation showed no change. These data indicate that although DHA treatment results in an unexpected increase in EGFR phosphorylation, aspects of downstream signaling are suppressed. This could, in part, explain why fish oil feeding promotes colonocyte apoptosis and inhibits tumor growth. This work was supported in part by NIH grants CA59034, P30ES09106. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 276.

published proceedings

  • Cancer Research

author list (cited authors)

  • Turk, H. F., Lupton, J. R., & Chapkin, R. S.

complete list of authors

  • Turk, Harmony F||Lupton, Joanne R||Chapkin, Robert S

publication date

  • January 1, 2010 11:11 AM