| Project/Area Number |
03807019
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Okayama University |
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Principal Investigator |
KANO Yoshio Department of Cell Biology, Okayama University Medical School Research Associate, 医学部, 助手 (70116200)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | human fibroblasts / Wilms' tumor patients / Cellular aging / abnormal crisis / SV40T / senescent genes / C-1 gene / Immortalization / DNAのメチル化 / テロメラーゼ / 老化蛋白のリン酸化 / ヒト細胞 / 突然変異 / クロ-ニング / cDNAライブラリ- / 発現ベクタ- |
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| Research Abstract |
Normal human diploid fibroblasts have a limited proliferative capacity in vitro. In contrast, cells derived from tumors often exhibit unlimited proliferative potential (immortality). Immortalization of the human cells is associated with the process of cellular aging. We established an immortalization sensitive cell line from the fibroblasts of Wilms' tumor patients with a partial deletion of chromosome 11p. This cell line showed 50 times higher imortalization frequency than normal human fibroblasts immortalized by SV40T. This type of 11p-cells which produced SV40T protein showed an abnormal crisis at the senescent period, whereas T-antigen positive normal cells did not. The crisis culture of this 11p-cells showed a extremely higher frequency of spontaneous mutation and chromosomal aberrations than normal cells. By differential hybridization, we tried to identify the human genes that would be preferentially expressed in 11p-cells at the time of the crisis, and obtained a clone, C-1 gene, that was up-regulated in the senescent cells. A partial loss of C-1 gene was found in some kinds of immortal cells. These results indicate that the inactivation of senescent genes at the crisis phase of the cellular aging may be associated with the cellular immortalization.
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