Document Detail


Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line.
MedLine Citation:
PMID:  18427553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Barrett's epithelium is a precancerous, specialized columnar metaplasia in the distal esophagus. We demonstrate the changes in cellular phenotype in a non-neoplastic Barrett's cell line (BAR-T), following exposure to acid and bile salt, the two important components of gastroesophageal refluxate. Cell phenotypes in BAR-T cell line were quantified by fluorescence-activated cell sorting (FACS) using monoclonal antibodies against markers: cytokeratin 8/18 (CK8/18) for columnar, CK4 for squamous, mAbDas-1 for colonic epithelial cell phenotype and p75NTR for esophageal progenitors. Cells were exposed for 5 min each day to 200 microM glycochenodeoxycholic acid at pH 4, pH 6 and pH 7.4 or only to acid (pH 4) for up to 6 weeks. The BAR-T cell line comprised 35+/-5.2% CK8/18, 32+/-3.5% mAbDas-1, 9.5+/-3% CK4 and 4+/-2.5% p75NTR-positive cells. Single exposure to acid and or bile did not change cell phenotypes. However, chronic treatment for at least 2 weeks significantly enhanced (P<0.05) the expression of colonic phenotype and CK8/18-positive cells, as evidenced by FACS analysis. Bile salt at pH 4 and bile salt followed by acid (pH 4) in succession were the strongest stimulators (P<0.01) for induction of colonic phenotype cells. Squamous (CK4(+)) phenotype did not change by the treatments. Cox-2 expression was induced after acute treatment and increased to twofold during chronic treatment, particularly in response to acidic pH. We conclude that BAR-T cells can be utilized as an 'in vitro' model to study the effect of environmental factors and their influence on the cellular phenotype and molecular changes in the pathogenesis of esophageal cancer.
Authors:
Manisha Bajpai; Jianying Liu; Xin Geng; Rhonda F Souza; Peter S Amenta; Kiron M Das
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural     Date:  2008-04-21
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  88     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-23     Completed Date:  2008-06-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  643-51     Citation Subset:  IM    
Affiliation:
Division of Gastroenterology and Hepatology, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / metabolism
Barrett Esophagus / metabolism*,  pathology,  ultrastructure
Bile Acids and Salts / pharmacology*
Cell Line, Transformed
Colon* / drug effects,  metabolism,  pathology
Epithelial Cells / drug effects,  metabolism*,  pathology
Flow Cytometry
Humans
Hydrogen-Ion Concentration
Immunohistochemistry
Keratin-18 / metabolism
Keratin-4 / metabolism
Keratin-8 / metabolism
Phenotype
Time Factors
Grant Support
ID/Acronym/Agency:
R01DK063618/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Bile Acids and Salts; 0/Keratin-18; 0/Keratin-4; 0/Keratin-8

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