| Project/Area Number |
15580081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KATAKURA Yoshinori Kyushu Univ., Fac, Agriculture, Associate Professor, 大学院・農学研究院, 助教授 (50264106)
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| Co-Investigator(Kenkyū-buntansha) |
TERUYA Kiichiro Kyushu Univ., Fac, Agriculture, Research Associate, 大学院・農学研究院, 助手 (10273971)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Cellular senescence / Telomerase / TAK1 / Protein Kinase C / Tumor suppression / 創薬ターゲット / PKC-δ / テロメア |
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| Research Abstract |
1.Evaluation of cellular senescence inducing ability of hTERT repressers : We clarified that hTERT repressors, TGF-β,TAK1 and PKC-δ, induce cellular senescence in human normal diploid cells.
2.Evaluation of tumorigenicity of cellular senescence inducing factors : We clarified that TGF-β demonstrated anti-tumor ability against human adenocarcinoma cells both in vitro and in vivo, suggesting that cellular senescence would functions as tumor suppressor mechanism.
3.Gene expression profile analysis of cellular senescence mechanisms : We investigated gene expression profile analysis of cells exposed to various cellular senescence inducing factors. As a result of clustering analysis, we found that cellular senescence inducing signals have in common with aging inducing signals.
4.Analysis of regulation mechanisms of human telomerase reverse transcriptase gene promoter : We demonstrated a repression mechanisms of hTERT promoter induced by TAK1.
5.Molecular mechanisms of functional impairment of telomerase in sublines derived from human adenocardnoma exposed to mild oxidative stress. We established novel cell lines named AST cells, which demonstrate a telomere shortening dependent upon the number of cell devisions despite of strong telomerase activity. This functional impairment of tebmerase was found to be due to cytoplasmic retentiono f telomerase in AST cells.
6.Regulation mechanisms of mouse telomerase reverse transcriptase(mTERT) gene promoter : We identified novel transcription factor that functions in the activation of mTERT promoter.
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