The Bile Acid Nuclear Receptor FXR and the Bile Acid Binding Protein IBABP Are Differently Expressed in Colon Cancer
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- De Gottardi, A., Touri, F., Maurer, C.A. et al. Dig Dis Sci (2004) 49: 982. doi:10.1023/B:DDAS.0000034558.78747.98
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Bile acids have been implicated in the development of colorectal cancers. We investigated the ex-pressionof the transcription factor regulated by bile acids, farnesoid X receptor (FXR), as well asother components of this pathway in human colorectal tumors and cell lines. The most significantchanges were a decrease in FXR mRNA levels in adenomas (5-fold average) and carcinomas (10fold average) and an increase in peroxisome proliferator activated receptor-γ (2-fold average). FXRwas not expressed in undifferentiated colon adenocarcinoma SW480 cells and metastasis derivedSW620 cells. In Caco-2 and HT-29 cells, the level of FXR expression increased with the degree ofdifferentiation. Intestinal bile acid binding protein was activated by chenodeoxycholic acid and thesynthetic FXR agonist GW4064 in Caco-2 and HT-29 but not in SW cells unless FXR was trans-fected.The down-regulation of the nuclear receptor FXR in colon cancer might be of clinical andpharmacological importance.