Increased dietary fat is correlated with colon cancer, and one possible reason is that high-fat diets increase excretion of bile acids. The bile acids are ligands for the farnesoid X receptor (FXR), a nuclear receptor that regulates bile-acid homeostasis. In this issue, Maran et al. show that FXR deficiency in mice leads to increased intestinal proliferation and tumor development. The authors investigated the role of FXR using adenomatous polyposis coli mutant (APCmin) mice and azoxymethane treatment, which causes polyps to develop in the small intestine and the colon, respectively. It was found that FXR is located predominantly in the epithelial cell nucleus and the apical region of the crypts. Two-month-old FXR knockout mice showed increased bromodeoxyuridine labeling in the colon and increased numbers of apoptotic cells. Generation of FXR deficiency in APCmin mice resulted in increased multiplicity and size of adenomas, and FXR deficiency significantly increased adenocarcinoma prevalence after azoxymethane treatment. It was also found that FXR deficiency increases lymphoid nodules in small intestine and colon. The results demonstrate that loss of FXR function increases susceptibility of intestinal cells to proliferative stimuli and that treatment with FXR ligands could aid in the treatment of colon cancer.
See article at J Pharmacol Exp Ther 2009, 328:469–477.
- The American Society for Pharmacology and Experimental Therapeutics