title: Alternative lengthening of telomeres is induced by telomerase inhibitors             in Barrett's esophageal cells.
abstract: A crucial step in the path to the malignant transformation of cells and             tumor formation is immortalization, which essentially depends on telomere maintenance.             The aim of this study was to investigate the role of telomerase in the progression             of Barrett's esophagus. Telomerase activity was measured in Barrett's cells using             terminal restriction fragment (TRF) analysis. Telomere length was measured using             Q-FISH analysis. Furthermore, the telomere recombination events were detected             between sister chromatids using chromosome orientation FISH (CO-FISH). There was             a reduction in telomerase activity in the CP-A cells transduced with MT-hTER/47A+siRNA,             which led to an almost complete disappearance of telomerase activity. The telomere             length of the CP-A cells transduced with MT-hTER/47A+siRNA was slightly shorter             compared to that of the untransduced cells. The telomerase-inhibited cells were             morphologically indistinguishable from those untransduced and WT-hter-transduced             cells. In the control cells, the growth rate was between 0.9 to 1.1 with the population             doubling per day. Although the transduction of the telomerase inhibitors in the             CP-A cells did not cause a significant reduction in cell growth, these transduced             cells grew generally slower compared with the control cells. The heterogeneous             telomere length was also be detected in the telomerase-inhibited CP-A cells. However,             the telomere length remained homogeneous in the control cells. The metaphase of             the CP-A cells transduced with MT-hTER/47A+siRNA demonstrated 70% heterogeneous             telomeres. In addition, no increased recombination was observed between sister             chromatids in the transduced CP-A cells compared with the control cells. Our findings             suggest that an alternative lengthening of telomeres (ALT) may be induced by telomerase             inhibitors in CP-A cells. Therefore, telomerase inhibitors may exhibit high potency             in the treatment of esophageal adenocarcinoma arising from Barrett's esophagus.
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, PR China.
authors: Xiuguang
authors: X
authors: Qin
authors: Bo
authors: B
authors: Qi
authors: Baosheng
authors: B
authors: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D034741:RNA, Small Interfering / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000187:drug effects / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D019098:Telomerase