Document Detail

Inflammatory mediators of esophagitis alter p27 Kip1 expression in esophageal epithelial cells.
MedLine Citation:
PMID:  20818264     Owner:  NLM     Status:  In-Process    
BACKGROUND: Barrett esophagus (BE) is a premalignant condition that develops due to prolonged gastroesophageal reflux disease (GERD). In some but not all cases, BE progresses to Barrett-associated adenocarcinoma. p27 is a tumor-suppressor protein that regulates the cell's division cycle and appears to be frequently inactivated in Barrett-associated adenocarcinoma due to increased degradation or cytoplasmic mislocalization. Reduced or mislocalized p27 would remove it from its nuclear targets and result in increased proliferation. Although bile acid and hydrochloric acid (HCl) are linked to the pathogenesis of BE, not every patient with BE has a history of GERD. Eosinophilic esophagitis mimics GERD, but eosinophil granule proteins, known to mediate inflammation, have not been linked to BE. It was unknown whether mediators of esophagitis affect p27 expression and/or localization in normal esophageal cells. We assessed the effects of bile acid, HCl, and eosinophil granule proteins on p27 protein expression, localization, and its ability to regulate cell proliferation.
MATERIALS AND METHODS: Human esophageal epithelial (HET-1A) cells were incubated with chenodeoxycholic acid (CDC), HCl, and eosinophil granule proteins (major basic protein, MBP; and eosinophil peroxidase, EPO). Cell viability analysis, immunoblot, immunofluorescence microscopy, and flow cytometric analysis were performed.
RESULTS: Exposure of HET-1A cells to CDC, HCl, MBP, and EPO did not affect total p27 levels. CDC, HCl, MBP, and EPO caused mislocalization of p27 from the nucleus to the cytoplasm. Flow cytometry showed that CDC exposure also increased HET-1A cell proliferation.
CONCLUSIONS: Mislocalization of p27 caused by mediators of GERD or eosinophilic esophagitis may serve as an early marker of increased cell proliferation, which may contribute to the risk for esophageal dysplasia.
Kim-Doan Katrina Nguyen; Stacy W Blain; Frank Gress; William R Treem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pediatric gastroenterology and nutrition     Volume:  51     ISSN:  1536-4801     ISO Abbreviation:  J. Pediatr. Gastroenterol. Nutr.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8211545     Medline TA:  J Pediatr Gastroenterol Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  556-62     Citation Subset:  IM    
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, SUNY Downstate Medical Center, Brooklyn, NY, USA.
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