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The Bile Acid Nuclear Receptor FXR and the Bile Acid Binding Protein IBABP Are Differently Expressed in Colon Cancer

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Abstract

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.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University Hospital, Geneva

    Andrea De Gottardi

  2. ILEX Oncology Research, Versoix

    Fethi Touri, Anne Perez, Oliver Maurhofer, Giovanni Ventre, Craig L. Bentzen & Eric J. Bentzen

  3. Department of Surgery, Kantonsspital, Liestal

    Christoph A. Maurer

  4. Department for Clinical Pharmacology, University of Bern, Bern, Switzerland

    Jean-Francois Dufour

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  1. Andrea De Gottardi
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  2. Fethi Touri
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  3. Christoph A. Maurer
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  4. Anne Perez
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  5. Oliver Maurhofer
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  7. Craig L. Bentzen
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  9. Jean-Francois Dufour
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De Gottardi, A., Touri, F., Maurer, C.A. et al. The Bile Acid Nuclear Receptor FXR and the Bile Acid Binding Protein IBABP Are Differently Expressed in Colon Cancer. Dig Dis Sci 49, 982–989 (2004). https://doi.org/10.1023/B:DDAS.0000034558.78747.98

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  • DOI: https://doi.org/10.1023/B:DDAS.0000034558.78747.98

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