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人端粒酶逆转录酶(hTERT)是端粒酶活性的限速因子,因此hTERT活性调控被认为是人端粒酶活性调节的一个主要机制。目前有关hTERT活性调控的研究主要集中在hTERT基因转录水平。研究表明已知的几种转录因子、细胞分化诱导剂、某些病毒相关蛋白以及DNA甲基化和乙酰化状态可能在转录水平对hTERT表达起调控作用。 相似文献
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端粒酶表达是恶性肿瘤发生、发展的主要机制,其组分之一人端粒酶逆转录酶(hTERT)激活是端粒酶表达的限速步骤,决定着端粒酶活性的高低。hTERT的激活表达又受多种因素调控,特别是其启动子区甲基化。本文对近年来hTERT基因启动子区甲基化的状态、位点、作用及临床意义等研究作一概述。 相似文献
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目的:探讨人胃腺癌细胞系SGC7901及其多药耐药亚系SGC7901/VCR中端粒酶活性变化及其机制,为胃癌多药耐药机制研究提供新靶点。方法:采用TRAP银染方法检测SGC7901和SGC7901/VCR中端粒酶的活性;应用反转录聚合酶链反应(RT—PCR)技术检测SGC7901和SGC7901/VCR中端粒酶hTERT、Madl及c—myctuRNA的表达;将hTERT启动子构建的报告基因质粒(pGL3B—TRTP),转染入SGC7901和SGC7901/VCR中,应用双荧光素酶报告基因检测系统(Dual—Luciferasereporterassaysystem)检测端粒酶hTERT启动子的活性。结果:SGC7901/VCR细胞中的端粒酶活性及端粒酶hTERTmRNA表达均显著高于SGC7901细胞,且SGC7901/VCR中hTERT启动子的活性显著高于SGC7901,在SGC7901/VCR中捡测到c—mycmRNA的表达,但未检测到MadlmRNA的表达,而在SGC7901细胞中分别检测到MadlmRNA和c—mycmRNA的表达,且SGC7901细胞中c—mycmRNA的表达也高于SGC7901/VCR。结论:端粒酶活性及端粒酶hTERT转录水平升高与胃癌细胞的多药耐药性密切相关,转录因子Madl/c—myc的表达高低是其作用机制之一。 相似文献
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多西紫杉醇对人胃癌细胞BGC-823 hTERT启动子转录活性及其调控基因c-myc表达的研究 总被引:1,自引:0,他引:1
目的:探讨多西紫杉醇对人胃癌细胞BGC-823端粒酶活性和端粒酶逆转录酶(hTERT)mRNA表达、hTERT启动子转录活性及其转录调控基因c-myc蛋白表达的影响。方法:加药多西紫杉醇24、48和72h后收集细胞,MTT比色法测定IC50值;分别采用PCR-ELISA法检测端粒酶活性和RT-PCR法检测端粒酶逆转录酶hTERT mRNA的表达;Luciferase法检测hTERT启动子活性;Western blot技术检测c-myc蛋白的表达。结果:多西紫杉醇可以明显抑制胃癌细胞BGC-823的端粒酶活性和hTERT mRNA的表达,呈一定的时效、量效关系;进一步研究发现,多西紫杉醇对胃癌细胞端粒酶活性的影响抑制了hTERT启动子转录活性的表达,同时对启动子转录活性调控蛋白c-myc表达的研究也证实了这一点。结论:hTERT mRNA的表达与胃癌的发生和演进有关,癌基因c-myc可能通过参与hTERT启动子转录活性的表达调控而调控hTERT mRNA表达。多西紫杉醇抑制胃癌细胞BGC-823的增殖可能与其抑制BGC-823细胞hTERT启动子转录活性和c-myc蛋白表达相关。 相似文献
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目的 探讨肺癌组织中端粒酶基因hTR、hTERT与端粒酶活性的表达是否与肺癌的发生发展有关,深入了解端粒酶基因对端粒酶活性的调控是在基因水平还是在转录水平。方法 采用TRAP-PCR和RT-PCR方法分别检测68例肺癌组织及相应癌旁肺组织中端粒酶活性、端粒酶基因hTR和hTERP的表达。结果 68例肺癌组织中端粒酶阳性率为79.4%(54/68),hTR阳性率为98.5%(67/68),hTERT阳性率为91.2%(62/68)。68例癌旁组织中无一例表达端粒酶阳性,但大多数癌旁组织均表达hTR(62/68,91.2%),仅7例hTERT表达阳性(10.3%),与hTR相比,hTERT同端粒酶具有更高的一致性,其一致率为89.0%(121/136),而ThTR与端粒酶的一致率为43.4%(59/136)。结论 端粒酶的活性可能在肺癌发生发展中起重要的作用。hTR与hTERT可能是在转录后或翻译后水平对端粒酶进行调控的。 相似文献
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Saito M Nakagawa K Hamada K Hirose S Harada H Kohno S Nagato S Ohnishi T 《International journal of oncology》2004,24(5):1213-1220
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Kirch HC Ruschen S Brockmann D Esche H Horikawa I Barrett JC Opalka B Hengge UR 《Oncogene》2002,21(52):7991-8000
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HIF-1-mediated activation of telomerase in cervical cancer cells 总被引:10,自引:0,他引:10
Yatabe N Kyo S Maida Y Nishi H Nakamura M Kanaya T Tanaka M Isaka K Ogawa S Inoue M 《Oncogene》2004,23(20):3708-3715
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Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity 总被引:10,自引:0,他引:10
Guilleret I Yan P Grange F Braunschweig R Bosman FT Benhattar J 《International journal of cancer. Journal international du cancer》2002,101(4):335-341
DNA methylation is an epigenetic process involved in embryonic development, differentiation and aging. It is 1 of the mechanisms resulting in gene silencing in carcinogenesis, especially in tumor suppressor genes (e.g., p16, Rb). Telomerase, the DNA polymerase adding TTAGGG repeats to the chromosome end, is involved in the regulation of the replicative life span by maintaining telomere length. This enzyme is activated in germ and stem cells, repressed in normal somatic cells and reactivated in a large majority of tumor cells. The promoter region of the hTERT gene, encoding for the catalytic subunit of human telomerase, has been located in a CpG island and may therefore be regulated at least in part by DNA methylation. We analyzed the methylation status of 27 CpG sites within the hTERT promoter core region by methylation-sensitive single-strand conformation analysis (MS-SSCA) and direct sequencing using bisulfite-modified DNA in 56 human tumor cell lines, as well as tumor and normal tissues from different organs. A positive correlation was observed among hypermethylation of the hTERT promoter, hTERT mRNA expression and telomerase activity (p < 0.00001). Furthermore, this correlation was confirmed in normal tissues where hypermethylation of the hTERT promoter was found exclusively in hTERT-expressing telomerase-positive samples and was absent in telomerase-negative samples (p < 0.00002). Since tumor tissues contain also nonneoplastic stromal elements, we performed microdissection to allow confirmation that the hTERT promoter methylation truly occurred in tumor cells. Our results suggest that methylation may be involved in the regulation of hTERT gene expression. To our knowledge, this is the first gene in which methylation of its promoter sequence has been found to be positively correlated with gene expression. 相似文献
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Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells 总被引:33,自引:0,他引:33
Xu D Wang Q Gruber A Björkholm M Chen Z Zaid A Selivanova G Peterson C Wiman KG Pisa P 《Oncogene》2000,19(45):5123-5133