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Query: UMLS:C0154059 (Esophagus)
 2,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Dis Esophagus 2007
PMID:Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell line (BAR-T). 1750 24

Barrett's specialized columnar epithelium (SCE) replaces reflux-damaged squamous epithelium. The benefits of SCE lie in its superior protection of the esophagus against further reflux damage. It was shown that this protection is dependent on ion transport and barrier function of SCE. The risks of SCE lie in its higher predisposition to malignant transformation. An understanding of underlying mechanisms of both processes would benefit considerably from greater knowledge of the structure and function of native SCE - the latter recently advanced by the availability of a telomerase-immortalized, nonneoplastic, human Barrett's cell line (BAR-T). Some of BAR-T characteristics for growth and differentiation have been described recently, but not its capacity to serve as a model for ion transport and barrier function of SCE. To determine the latter, BAR-T cells were grown in enriched media, seeded on permeable supports, and subjected to electrical, biochemical, and morphologic study. HET-1A (esophageal epithelial cell line), a nonneoplastic, human esophageal squamous cell line, was also studied for comparison. BAR-T, but not HET-1A cells in HEPES Ringer solution behaved as polarized monolayers with the capacity for ion transport and barrier function. This was evident electrically with a volt-ohm meter (EVOM),which recorded in BAR-T a resting potential difference of 2.0 +/- 0.2 mV, Isc of 17.4 +/- 3.3 microAmps/cm2 and resistance of 103 +/- 12 ohms x cm2. Further, Isc in BAR-T was inhibitable by exposure to Na-free solution, serosal ouabain, and luminal 4-acetamido4'-isothiocyano-2,2'-stilbenedisulfonic acid. Expression of tight junction genes were determined in BAR-T and HET-1A cells using quantitative reverse transcriptase-polymerase chain reaction, with expression of zonula occludens-1 (ZO-1) set at 1 as reference. Claudins 1, 4, and 12 were prominently expressed in BAR-T (0.2-0.6 of ZO-1), while claudins 1, 11, and 12 were prominently expressed in HET-1A(0.1-0.8 of ZO-1). BAR-T, but not HET-1A, expressed claudins 4, 8, 16, 18, and 23, and HET-1A, but not BAR-T, expressed claudins 11, 15, and 20. Protein expression of prominently expressed claudins in BAR-T correlated with mRNA expression. Immunofluorescence and confocal microscopy localized claudins 1 and 4 in BAR-T to cell membranes and claudin 18, specifically to the tight junction. Membrane polarization was also documented in BAR-T by immunolocalization of NaK,ATPase to the basolateral membrane. BAR-T, but not HET-1A cells grown on permeable supports form a polarized monolayer with both ion transport and barrier function. Since a number of features of BAR-T are similar to Barrett's SCE and distinct from HET-1A, the BAR-T cell line represents a valuable resource for the study of ion transport and barrier function of nondysplastic SCE.
Dis Esophagus 2009
PMID:Ion transport and barrier function in a telomerase-immortalized human nondysplastic, Barrett's cell line (BAR-T). 1967 46