Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor

Increased dietary fat consumption is associated with colon cancer development. The exact mechanism by which fat in-duces colon cancer is not clear, however, increased bile acid excretion in response to high-fat diet may promote colon car-cinogenesis. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, and bile acids are endogenous ligands of FXR. FXR is highly expressed in the intestine and liver where FXR is essential for maintaining bile acid homeostasis. The role of FXR in intestine cancer development is not known. The current study evaluated the effects of FXR deficiency in mice on intestinal cell proliferation and cancer development. The results showed that FXR deficiency resulted in increased colon cell proliferation, which was accompanied by an up-regulation in the expression of genes involved in cell cycl