Abstract 5590: Role of estrogen receptor-beta in colitis-associated cancer

Abstract

Abstract Inflammatory bowel disease has been strongly correlated with colitis-associated cancer (CAC) cases, a subtype of colorectal cancer. Previously, we demonstrated that estrogen receptor-beta (ERβ) exerted protective effects against the development of colonic precancerous lesions in the azoxymethane-induced spontaneous colon cancer in vivo model. In the present study, we investigated whether ERβ could also be protective against CAC. Estrogen receptor-β knockout (βERKO) and wild type (WT) mice were exposed to azoxymethane, followed by dextran sodium sulfate (DSS) treatment. Three days after the DSS treatment two βERKO mice died, suggesting that these mice might be more susceptible to inflammatory inducers than WT mice. Furthermore, six weeks after DSS exposure five mice from each group were sacrificed and morphology and RNA analyses of inflammation markers were performed. All βERKO mice presented polyp-like structures in the colon (3.60 ± 0.81) and greater number of cellular infiltration areas (9.00 ± 1.50), whereas only two WT mice presented polyp-like structures (2.40 ± 1.47) and fewer number of cellular infiltration areas (4.00 ± 2.02). βERKO mice showed 9.8 and 5.6 fold increase in mRNA expression of inducible-nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), respectively, when compared to WT mice. In both βERKO and WT mice a 2.1 fold increase in cyclooxygenase-2 (COX-2) mRNA expression was observed compared to the respective negative control groups. All together these results suggest that ERβ might be protective against CAC. These data will be compared to the group of mice that will be sacrificed 15 weeks post DSS treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5590. doi:10.1158/1538-7445.AM2011-5590