The Role of p53 and Estradiol on the Suppression of Sporadic Tumor Formation in the Colon

Abstract

Previous studies have shown a correlation between estradiol (E2) levels in women and the decreased risk of colon cancer. E2 serves a protective role in the colon by increasing apoptosis in non-malignant colonocytes that have become damaged due to different stressors within the body. The p53 protein plays an important role at the cellular level by detecting DNA damage and regulating cell cycle progression. A proposed mechanism suggested by in vitro studies, indicates that the protective effects of E2 on tumor formation within the colon is mediated by p53. The roles of E2 and p53 on tumor development in the colon were analyzed through the identification of visible tumors and proliferation in the distal colons of C57/BL-6J female mice. E2 suppressed tumor development in the presence of a functional p53 protein. Proliferation was enhanced in colonic tissue lacking a functional p53, thus suggesting the importance of p53 in suppressing tumor development. Collectively, our findings illustrate the importance of a functional p53 protein in tumor development and its role in mediating E2 protective effects within the colon.