| Project/Area Number |
14370745
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
IDE Toshinori Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (60012746)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2002: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | telomere / telomerase / proteome / gene expression / fibroblasts / 繊維芽細胞 / 乳腺上皮細胞 / プロテオーム / ウイルスベクター |
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| Research Abstract |
Telomerase is known as an enzyme that elongates telomere DNA at each chromosome end of eukaryotic cells providing cells indefinite proliferative lifespan. However, our results suggested that telomerase participated more than that in telomerase-expressing human somatic cells. Some human somatic cells in vitro continue proliferation to the limit of telomere shortening and ceased proliferation by cellular senescence but other somatic cells cease proliferation by culture shock or premature senescence far before telomere shortening. These human somatic cells can proliferate to the final end of telomere erosion after the introduction of T-antigen gene whose gene product inactivates tumor suppressor gene products as p53 and RB. Unexpectedly, introduction of telomerase gene (hTERT) into human somatic cells also extended proliferative lifespan and sometimes made cells immortal (infinite proliferative lifespan). We searched for cellular proteins, by proteome analysis, that facilitated cells for continued proliferation in telomerase introduced human somatic cells. We identified many proteins, by MAS analysis, from 2D-gel spots that were increased or decreased after introduction of hTERT. Role of these proteins on lifespan extension will be examined. Other possible role of telomerase is on genome integrity. Telomerase-introduced human somatic cells showed resistance against chromosome aberration and integration of exogenous genetic materials. These characteristics are favorable for the function of somatic stem cells, which harbor telomerase activity, to continue proliferation during whole human lifespan and to maintain low tumorigenicity.
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