Research

Expression of the bile acid receptor FXR in Barrett's esophagus and enhancement of apoptosis by guggulsterone in vitro

Andrea De Gottardi¹ , Jean-Marc Dumonceau¹ , Fabien Bruttin¹ , Alain Vonlaufen¹ , Isabelle Morard¹ , Laurent Spahr¹ , Laura Rubbia-Brandt² , Jean-Louis Frossard¹ , Winand NM Dinjens³ , Peter S Rabinovitch⁴ and Antoine Hadengue¹

¹  Division of Gastroenterology, University Hospital, Micheli-du-Crest 24, 1205 Geneva, Switzerland

²  Division of Clinical Pathology, University Medical Centre, Michel Servet 1, 1211 Geneva, Switzerland

³  Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

⁴  Department of Pathology, 1959 NE Pacific Avenue HSB K-081, Box 357470, Seattle, Washington 98195-7705 USA

author email corresponding author email

Molecular Cancer 2006, 5:48doi:10.1186/1476-4598-5-48

Published:	20 October 2006

Abstract

Background

Barrett's esophagus, a risk factor for esophageal adenocarcinoma, is associated with reflux disease. The aim of this study was to assess the expression of bile acid receptors in the esophagus (normal, esophagitis, Barrett's esophagus and adenocarcinoma) and to investigate their possible function.

Results

the expression of the bile acid receptors FXR and VDR in esophageal biopsies from patients with a normal mucosa, esophagitis, Barrett's esophagus or adenocarcinoma (n = 6 per group) and in cell lines derived from Barrett's esophagus and esophageal adenocarcinoma, was assessed by real time Q-PCR and immunohistochemistry. The effect of guggulsterone, an antagonist of bile acid receptors, on apoptosis of Barrett's esophagus-derived cells was assessed morphologically, by flow cytometry and by measuring caspase 3 activity.

The expression of FXR was increased in esophagitis, Barrett's esophagus and adenocarcinoma compared to normal mucosa by a mean of 44, 84 and 16, respectively. Immunohistochemistry showed a weak expression in normal esophagus, a strong focal reactivity in Barrett's esophagus, and was negative in adenocarcinoma. VDR expression did not significantly differ between groups. In cell cultures, the expression of FXR was high in Barrett's esophagus-derived cells and almost undetectable in adenocarcinoma-derived cells, whereas VDR expression in these cell lines was not significantly different. In vitro treatment with guggulsterone was associated with a significant increase in the percentage of apoptotic cells and of the caspase 3 activity.

Conclusion

the bile acid receptor FXR is significantly overexpressed in Barrett's esophagus compared to normal mucosa, esophagitis and esophageal adenocarcinoma. The induction of apoptosis by guggulsterone in a Barrett's esophagus-derived cell line suggests that FXR may contribute to the regulation of apoptosis.