Document Detail


Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell line (BAR-T).
MedLine Citation:
PMID:  17509124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Barrett's esophagus, a metaplasia predisposed to malignant transformation, has been studied in vitro using esophageal adenocarcinoma cell lines. However, findings in such transformed cells may not be applicable to the non-neoplastic cells of benign Barrett's esophagus. Therefore, we have developed and characterized a Barrett's cell line derived from a patient without malignancy or dysplasia. Human Barrett's epithelial cells were immortalized with the insertion of hTERT (human telomerase reverse transcriptase) using a Cre-lox recombination system. We then examined properties of this continuous cell line, such as in vitro tumorigenicity, growth patterns, histological differentiation characteristics, karyotype, and checkpoint arrest mechanisms (e.g., p16, p21, and p53). Non-neoplastic Barrett's epithelial cells infected with hTERT (BAR-T cells) have been sustained in culture beyond 200 population doublings. BAR-T cells maintain a diploid chromosome number and exhibit non-neoplastic properties, such as contact inhibition and anchorage-dependent growth. BAR-T cells express differentiation Barrett's epithelial markers, such as villin and cytokeratins 4, 8 and 18, and stain positive for Alcian blue, indicating the presence of mucin-producing cells. Expression of checkpoint arrest proteins p21 and p53 are intact, while p16 expression is lost. Thus, we have created a human Barrett's cell line that is not malignantly transformed, and yet can be maintained indefinitely in culture. BAR-T cells are diploid, have histological differentiation markers characteristic of benign Barrett's epithelium, and also maintain appropriate expression of p21 and p53. This cell line should be a useful model for the study of the early events in carcinogenesis in Barrett's esophagus.
Authors:
K R Jaiswal; C P Morales; L A Feagins; K G Gandia; X Zhang; H-Y Zhang; K Hormi-Carver; Y Shen; F Elder; R D Ramirez; G A Sarosi; S J Spechler; R F Souza
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E     Volume:  20     ISSN:  1120-8694     ISO Abbreviation:  Dis. Esophagus     Publication Date:  2007  
Date Detail:
Created Date:  2007-05-18     Completed Date:  2007-09-18     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8809160     Medline TA:  Dis Esophagus     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  256-64     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Texas Southwestern Medical Center at Dallas and the VA North Texas Healthcare System, Dallas, TX 75216, USA.
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MeSH Terms
Descriptor/Qualifier:
Barrett Esophagus* / metabolism,  pathology
Cell Culture Techniques
Cell Line / pathology,  physiology*
Cell Survival
Contact Inhibition
Humans
Neoplasm Proteins / metabolism
Telomerase*
Telomere / physiology
Transduction, Genetic*
Grant Support
ID/Acronym/Agency:
5T32DK-07745/DK/NIDDK NIH HHS; DK63621/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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