| Project/Area Number |
13557138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kanazawa University |
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Principal Investigator |
KYO Satoru Kanazawa University, Obstetrics and Gynecology, Asist. Prof., 大学院・医学系研究科, 講師 (50272969)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Toshio Nippon Gene CO. Ltd, Research amd Reagent, Head Researcher, 研究試薬部, 製品開発課長(研究職)
INOUE Masaki Kanazawa University, Obstetrics and Gynecology, Prof., 大学院・医学系研究科, 教授 (10127186)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | Telomerase / Gene therapy / hTERT / hTR / Gynecologic tumors / 癌 |
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| Research Abstract |
We established novel methods that inhibit telomerase activity in cancer cells using 2-5Adenylate-linked antisense DNA against human telomerase RNA component (hTR). This antisense DNA effectively blocked telomerase activity in cervical cancer ME180 cells. Growth of ME180 cells in vitro was significantly inhibited by the treatment with 2-5A anti-hTR. Surprisingly, inhibition of cell growth was observed in 24-48 hr after treatment, quite earlier than expected. Telomere length was not shortened in this short period. These findings suggest that blockade of telomerase led to cell growth inhibition via telomere-independent mechanisms. We confirmed that growth inhibition of cells by the treatment with 2-5A anti-hTR was due to induction of apoptosis. The further anaylsis of mechanisms how 2-5A anti-hTR induces apoptosis is on going.
We also established novel vector system for cancer gene therapy. We previously cloned promoter of human telomerase reverse transcriptase (hTERT), which is highly specific to cancer cells. We thus used this promoter for cancer-specific gene expression in gene delivery system. Various apoptosis-inducible genes, such as caspase-8 and FADD, were combined with hTERT promoter and used as vectors for cancer gene therapy. Introduction of these vectors effectively induced apoptosis of cancer cells but of surrounding normal tissues.
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