共查询到20条相似文献,搜索用时 31 毫秒
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hTERT associates with human telomeres and enhances genomic stability and DNA repair 总被引:16,自引:0,他引:16
Sharma GG Gupta A Wang H Scherthan H Dhar S Gandhi V Iliakis G Shay JW Young CS Pandita TK 《Oncogene》2003,22(1):131-146
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Jung Hwan Yoon Ho Seok Seo Won Seok Choi Olga Kim Suk Woo Nam Jung Young Lee Won Sang Park 《Oncotarget》2014,5(22):11695-11708
The present study aims to investigate whether gastrokine 1 (GKN1) induces senescence and apoptosis in gastric cancer cells by regulating telomere length and telomerase activity. Telomere length, telomerase activity, and hTERT expression decreased significantly in AGSGKN1 and MKN1GKN1 cells. Both stable cell lines showed increased expression of TRF1 and reduced expression of the hTERT and c-myc proteins. In addition, TRF1 induced a considerable decrease in cell growth, telomerase activity, and expression of hTERT mRNA and protein. GKN1 completely counteracted the effects of c-myc on cell growth, telomere length, and telomerase activity. Interestingly, GKN1 directly bound to c-myc and down-regulated its expression as well as inhibited its binding to the TRF1 protein and a hTERT promoter. Furthermore, GKN1 triggered senescence, followed by apoptosis via up-regulating the p53, p21, p27, and p16 proteins and down-regulating Skp2. Telomere length in 35 gastric cancers was shortened significantly compared with the corresponding gastric mucosae, whereas GKN1 expression was inversely correlated with telomere length and c-myc and hTERT mRNA expression. Taken together, these results suggest that GKN1 may shorten telomeres by acting as a potential c-myc inhibitor that eventually leads to senescence and apoptosis in gastric cancer cells. 相似文献
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Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells. 总被引:11,自引:0,他引:11
Telomerase is a promising target for human cancer gene therapy. Its inhibition allows telomere shortening to occur in cancer cells, which in turn is thought to trigger delayed senescence and/or apoptosis. We tested whether telomerase inhibition might have additional, immediate effects on tumor cell growth. Ovarian cancer cell lines with widely differing telomere lengths were efficiently transduced with an adenovirus expressing a ribozyme directed against the T motif of the catalytic subunit of human telomerase, hTERT. Three days after transduction, telomerase activity was significantly reduced and massive cell loss was induced in mass cultures from all four ovarian cancer cell lines tested, whereas transduction of telomerase-negative human fibroblasts did not attenuate their growth. The kinetics of induction of cell death in cancer cells was not significantly dependent on telomere length, and telomeres did not shorten measurably before the onset of apoptosis. The data suggest the existence of a "fast-track" mechanism by which diminution of telomerase can interfere with cancer cell growth and induce cell death, presumably by apoptosis. This phenomenon might be a consequence of the telomere capping function provided by telomerase in tumor cells. Uncapping of telomeres by ribozyme-mediated inhibition of telomerase bears therapeutic potential for ovarian cancer. 相似文献
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Role of human telomerase reverse transcriptase and telomeric-repeat binding factor proteins 1 and 2 in human hematopoietic cells. 总被引:12,自引:0,他引:12
K Yamada T Yajima A Yagihashi D Kobayashi Y Koyanagi K Asanuma M Yamada R Moriai H Kameshima N Watanabe 《Japanese journal of cancer research》2000,91(12):1278-1284
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Akiyama M Yamada O Kanda N Akita S Kawano T Ohno T Mizoguchi H Eto Y Anderson KC Yamada H 《Cancer letters》2002,178(2):187-197
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hTERT gene dosage correlates with telomerase activity in human lung cancer cell lines. 总被引:11,自引:0,他引:11
Gabriele Saretzki Simone Petersen Iver Petersen Konrad K?lble Thomas von Zglinicki 《Cancer letters》2002,176(1):81-91
Maintenance of telomeres, most often by telomerase, is a necessary prerequisite for immortality of eukaryotic cells. To better understand the mechanisms of telomerase up-regulation during tumorigenesis, we analysed the gene dosage of hTERT on chromosome 5p15, a region known to be overrepresented in a variety of malignancies, in 20 lung cancer cell lines by Southern blotting, fluorescence in-situ hybridization, and comparative genomic hybridization. We found a significant correlation between hTERT gene dosage, hTERT mRNA expression and telomerase activity. Imbalances of chromosome 5p may exert functionally relevant hTERT gene dosage effects in human lung cancer. 相似文献
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