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Identification of compounds that induce or repress telomerase activity

诱导或抑制端粒酶活性的化合物的鉴定

基本信息

批准号：
15590061
负责人：
TAHARA Hidetoshi
金额：
$ 2.18万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Telomerase activity was regulated by hTERT gene regulation. hTERT promoter (1.8kbp) was cloned into reporter vector which can monitoring hTERT transcription by green fluorescence or luciferase activity. Since normal fibroblasts have limited life span, normal fibroblasts need to be immortalized to using monitoring cells. hTERT gene was infected with retroviruses to immortalized cells. hTERT immortalized normal fibroblasts, NHF-hTERT and MRC-hTERT were used to generate hTERT transcription monitoring cells. We finally generated NHFT-TRP-Luc and MRCT-TRPLuc. We also constructed monitoring cell, RKO-TRPLuc, derived from telomerase positive cancer cells to screening anti-cancer drug targeted hTERT transcription. Using RKO-TRPluc cells, we screened natural compounds which suppress hTERT transcription in cancer cells, and 12 natural products were identified. Among them, two samples showed strong inhibition of hTERT transcription. These two compounds should be powerful anti-cancer activity. Further examination should be necessary to clarify the mechanism of these compounds.

端粒酶活性受hTERT基因调控。将hTERT启动子(1.8kbp)克隆到报告载体中，通过绿色荧光或荧光素酶活性监测hTERT的转录。由于正常成纤维细胞的寿命有限，因此需要利用监测细胞使正常成纤维细胞永生化。HTERT基因被逆转录病毒感染永生化细胞。用hTERT永生化的正常成纤维细胞、NHF-hTERT和MRC-hTERT构建hTERT转录监控细胞。最终得到NHFT-Trp-Luc和MRCT-TRPLuc。我们还构建了来自端粒酶阳性癌细胞的监测细胞RKO-TRPLuc，以筛选靶向hTERT转录的抗癌药物。利用RKO-TRPluc细胞，我们筛选出抑制癌细胞hTERT转录的天然化合物，并鉴定了12种天然产物。其中，两个样品对hTERT转录有较强的抑制作用。这两个化合物应该具有很强的抗癌活性。要弄清这些化合物的作用机理，还需要进一步的研究。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

G-quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells

DOI：
10.1038/sj.onc.1209217
发表时间：
2006-03-23
期刊：
ONCOGENE
影响因子：
8
作者：
Tahara, H;Shin-ya, K;Ide, T
通讯作者：
Ide, T

IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3.

DOI：
10.1016/j.bbrc.2005.09.036
发表时间：
2005-11
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
N. Tsuyama;I. Danjoh;K. Otsuyama;Masanori Obata;H. Tahara;T. Ohta;H. Ishikawa
通讯作者：
N. Tsuyama;I. Danjoh;K. Otsuyama;Masanori Obata;H. Tahara;T. Ohta;H. Ishikawa

G-tail telomere HPA : simple measurement of human single-stranded telomeric overhangs

G 尾端粒 HPA ：人类单链端粒突出的简单测量