Transcript Regulation of Human Telomerase Reverse Transcriptase by c-myc and mad1

被引:0
作者
Lin ZOU PengHui ZHANG ChunLi LUO ZhiGuang TU Faculty of Laboratory MedicineChongqing University of Medical SciencesChongqing China [400016 ]
机构
关键词
c-myc: mad1; hTERT promoter; transcript regulation;
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中图分类号
Q75 [分子遗传学];
学科分类号
071007 ;
摘要
<正> Telomerase activity is highly positive correlated to most malignant neoplasms.Human telomerasereverse transcriptase(hTERT)is the rate-limiting factor of telomerase activity.Recent studies have shownthat the expression of hTERT is mainly determined by its transcript regulation.Among the transcript regula-tion factors of hTERT,c-myc and mad 1 are well known.Here,we constructed c-myc and madl eukaryoticexpression vectors,then co-transfected them with the wild-type(Tw)or mutant hTERT promoter(Td)luciferase reporter plasmid,which were double-mutated in the E-box sequences from CACGTG to CACCTGof Tw.The change of luciferase activity in different cells was detected.The results showed that Tw wasobviously activated in T24 and EJ bladder cancer cells,but not in normal fibrocytes,c-myc and madl hadpositive and negative effects respectively on the Tw transcript in a dose-dependent manner,while the roles ofc-myc and madl in regulating the Td transcript were reversed,c-myc combined with madl can down-regulate Tw but not Td.These observations indicate that c-myc and madl can regulate the hTERT transcriptin a different manner in hTERT positive cells,but not in normal cells.This may provide an insight into sometelornerase-related carcinogenesis mechanisms.
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页码:32 / 38
页数:7
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[1]  
Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Madl .2 Gunes C,Lichtsteiner S,Vasserot AP,Englert C. Cancer Res . 2000