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Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
by
Pot, Raymond GJ
, Moons, Leon MG
, van Dekken, Herman
, Capello, Astrid
, van der Laan, Luc JW
, van de Winkel, Anouk
, Siersema, Peter D
, Menke, Vivianda
, Kusters, Johannes G
, Kuipers, Ernst J
in
Acids
/ Adenocarcinoma
/ Adenocarcinoma - genetics
/ Adenocarcinoma - pathology
/ Adult
/ Aged
/ Barrett Esophagus - genetics
/ Barrett Esophagus - pathology
/ Cancer
/ Case-Control Studies
/ Cell Line, Tumor
/ Cell Nucleus - metabolism
/ Cytoplasm - genetics
/ Diagnosis
/ Disease
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Esophagitis, Peptic - genetics
/ Esophagitis, Peptic - pathology
/ Esophagus - pathology
/ Female
/ Gastroenterology
/ Gene expression
/ Gene Frequency
/ Genetic aspects
/ Genotype
/ Hepatology
/ Humans
/ Immunohistochemistry
/ Internal Medicine
/ Male
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Polymorphism, Single Nucleotide
/ Real-Time Polymerase Chain Reaction
/ Receptors, Steroid - genetics
/ Research Article
/ Risk factors
/ RNA, Messenger - metabolism
/ Rodents
/ Throat
/ Translocation, Genetic
/ Young Adult
2011
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Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
by
Pot, Raymond GJ
, Moons, Leon MG
, van Dekken, Herman
, Capello, Astrid
, van der Laan, Luc JW
, van de Winkel, Anouk
, Siersema, Peter D
, Menke, Vivianda
, Kusters, Johannes G
, Kuipers, Ernst J
in
Acids
/ Adenocarcinoma
/ Adenocarcinoma - genetics
/ Adenocarcinoma - pathology
/ Adult
/ Aged
/ Barrett Esophagus - genetics
/ Barrett Esophagus - pathology
/ Cancer
/ Case-Control Studies
/ Cell Line, Tumor
/ Cell Nucleus - metabolism
/ Cytoplasm - genetics
/ Diagnosis
/ Disease
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Esophagitis, Peptic - genetics
/ Esophagitis, Peptic - pathology
/ Esophagus - pathology
/ Female
/ Gastroenterology
/ Gene expression
/ Gene Frequency
/ Genetic aspects
/ Genotype
/ Hepatology
/ Humans
/ Immunohistochemistry
/ Internal Medicine
/ Male
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Polymorphism, Single Nucleotide
/ Real-Time Polymerase Chain Reaction
/ Receptors, Steroid - genetics
/ Research Article
/ Risk factors
/ RNA, Messenger - metabolism
/ Rodents
/ Throat
/ Translocation, Genetic
/ Young Adult
2011
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Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
by
Pot, Raymond GJ
, Moons, Leon MG
, van Dekken, Herman
, Capello, Astrid
, van der Laan, Luc JW
, van de Winkel, Anouk
, Siersema, Peter D
, Menke, Vivianda
, Kusters, Johannes G
, Kuipers, Ernst J
in
Acids
/ Adenocarcinoma
/ Adenocarcinoma - genetics
/ Adenocarcinoma - pathology
/ Adult
/ Aged
/ Barrett Esophagus - genetics
/ Barrett Esophagus - pathology
/ Cancer
/ Case-Control Studies
/ Cell Line, Tumor
/ Cell Nucleus - metabolism
/ Cytoplasm - genetics
/ Diagnosis
/ Disease
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Esophagitis, Peptic - genetics
/ Esophagitis, Peptic - pathology
/ Esophagus - pathology
/ Female
/ Gastroenterology
/ Gene expression
/ Gene Frequency
/ Genetic aspects
/ Genotype
/ Hepatology
/ Humans
/ Immunohistochemistry
/ Internal Medicine
/ Male
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Polymorphism, Single Nucleotide
/ Real-Time Polymerase Chain Reaction
/ Receptors, Steroid - genetics
/ Research Article
/ Risk factors
/ RNA, Messenger - metabolism
/ Rodents
/ Throat
/ Translocation, Genetic
/ Young Adult
2011
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Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
Journal Article
Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma
2011
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Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Adult
/ Aged
/ Barrett Esophagus - genetics
/ Barrett Esophagus - pathology
/ Cancer
/ Disease
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Esophagitis, Peptic - genetics
/ Esophagitis, Peptic - pathology
/ Female
/ Genotype
/ Humans
/ Male
/ Medicine
/ Polymorphism, Single Nucleotide
/ Real-Time Polymerase Chain Reaction
/ Receptors, Steroid - genetics
/ Rodents
/ Throat
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