Gene/Protein Disease Symptom Drug Enzyme Compound
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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

The low affinity neurotrophin receptor p75NTR is known to be expressed in the mitotically quiescent basal layer (BL) of the normal esophageal epithelium. The aim of the present study was to detect oncogenic changes in the p75NTR-positive BL during esophageal squamous carcinogenesis. The normal epithelium (NE), low-grade intraepithelial neoplasia (LGN), high-grade intraepithelial neoplasia (HGN), and esophageal squamous carcinoma (SCC), in which invasion was limited to the muscularis mucosa, were obtained from surgically removed esophagi. The expression of p75NTR, the proliferation marker ki67, hTERT, p53, and p63 was examined immunohistochemically. The expression of p75NTR was detected in these tissues with average staining indexes (number of stained cells/100 nucleated cells; SI) of 1.00, 0.99, 0.81, and 0.73, respectively. The expression of ki67 in the BL significantly increased with the progression from LGN to HGN. The expression of hTERT and p53 significantly increased with the progression from NE to LGN, and then increased in a stepwise manner in HGN and SCC, with SI (hTERT/p53) of 0.10/0.11, 0.32/0.45, 0.50/0.72, and 0.65/0.61, respectively. The expression of p63 showed no significant difference among NE, LGN, HGN, and SCC, with SI of 0.82, 0.77, 0.85, and 0.87, respectively. A correlation was observed between the expression of ki67 and p53 (P = 0.005), while a negative correlation was found between p75NTR and hTERT (P = 0.01). Our results demonstrated that phenotypic changes from quiescent to active proliferation in the p75NTR-positive BL occurred during the progression from LGN to HGN. The altered expression of hTERT and p53 in the BL was detected in LGN, which suggested that additional oncogenic events that disrupt mitotic regulation in the p75NTR-positive quiescent BL may play a crucial role in malignant transformation. Further investigations using the isolation and tracing of p75NTR-positive cells in precancerous epithelia may provide us with a better understanding of squamous carcinogenesis.
Dis Esophagus 2015 Oct
PMID:Abnormal cell proliferation in the p75NTR-positive basal cell compartment of the esophageal epithelium during squamous carcinogenesis. 2488 22