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

DOI: 10.1186/1471-230x-11-108

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Abstract:

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.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).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.Persistent regurgitation of gastroduodenal contents into the lower esophagus causes mucosal injury manifested as reflux esophagitis (RE) [1,2]. As a complication of chronic RE, a Barrett's esophagus (BE) can develop [3,4]. BE is defined as an acquired condition in which the stratified squamous epithelium of the lower esophagus is replaced by specialized intestinal epithelium [5]. It is the sole commonly recognized risk factor for the development of esophageal adenocarcinoma (EAC) [6,7] and has an increasing incidence in the Western world [8]. While the importance of acid and bile exposure in the development of BE is well establish

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