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BMC Gastroenterology
Published in: BMC Gastroenterology 1/2011

Open Access 01-12-2011 | Research article

Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma

Authors: Anouk van de Winkel, Vivianda Menke, Astrid Capello, Leon MG Moons, Raymond GJ Pot, Herman van Dekken, Peter D Siersema, Johannes G Kusters, Luc JW van der Laan, Ernst J Kuipers

Published in: BMC Gastroenterology | Issue 1/2011

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Abstract

Background

The continuous exposure of esophageal epithelium to refluxate may induce ectopic expression of bile-responsive genes and contribute to the development of Barrett's esophagus (BE) and esophageal adenocarcinoma. In normal physiology of the gut and liver, the nuclear receptor Pregnane × Receptor (PXR) is an important factor in the detoxification of xenobiotics and bile acid homeostasis. This study aimed to investigate the expression and genetic variation of PXR in reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma.

Methods

PXR mRNA levels and protein expression were determined in biopsies from patients with adenocarcinoma, BE, or RE, and healthy controls. Esophageal cell lines were stimulated with lithocholic acid and rifampicin. PXR polymorphisms 25385C/T, 7635A/G, and 8055C/T were genotyped in 249 BE patients, 233 RE patients, and 201 controls matched for age and gender.

Results

PXR mRNA levels were significantly higher in adenocarcinoma tissue and columnar Barrett's epithelium, compared to squamous epithelium of these BE patients (P < 0.001), and RE patients (P = 0.003). Immunohistochemical staining of PXR showed predominantly cytoplasmic expression in BE tissue, whereas nuclear expression was found in adenocarcinoma tissue. In cell lines, stimulation with lithocholic acid did not increase PXR mRNA levels, but did induce nuclear translocation of PXR protein. Genotyping of the PXR 7635A/G polymorphism revealed that the G allele was significantly more prevalent in BE than in RE or controls (P = 0.037).

Conclusions

PXR expresses in BE and adenocarcinoma tissue, and showed nuclear localization in adenocarcinoma tissue. Upon stimulation with lithocholic acid, PXR translocates to the nuclei of OE19 adenocarcinoma cells. Together with the observed association of a PXR polymorphism and BE, this data implies that PXR may have a function in prediction and treatment of esophageal disease.
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Metadata
Title
Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
Authors
Anouk van de Winkel
Vivianda Menke
Astrid Capello
Leon MG Moons
Raymond GJ Pot
Herman van Dekken
Peter D Siersema
Johannes G Kusters
Luc JW van der Laan
Ernst J Kuipers
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2011
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-11-108

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