| Project/Area Number |
04836017
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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 |
老化(加齢)
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| Research Institution | Okayama University Medical School |
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Principal Investigator |
NAMBA Masayoshi Okayama University Inst.Cell.Mol.Med., Dept.Cell Biol., Professor, 医学部, 教授 (80069004)
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| Co-Investigator(Kenkyū-buntansha) |
KANO Yoshio Inst.Cell.Mol.Med., Dept.Cell Biol., Research Associate, 医学部, 助手 (70116200)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Human cell / Cellular aging / Immortalization / Cloning / 遺伝子 / 老化 |
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| Research Abstract |
Normal human cells are strongly destined for cellular aging. Elucidation of the mechanisms of cellular aging will shed light on the multistep processes of malignant transformation of human cells.
In order to overcome aging and to immortalize normal human cells, we had to treat the cells repeatedly with either 4NQO or Co-60 gamma rays. This indicates that the immortalization process involves multistep mutational events. The three immortalized cell lines we obtained showed mutation in p53, indicating that p53 may be involved in aging and immortalization process of human cells.
Thus we introduced the mutant p53 into normal human cells to learn whether or not the cells could be immortalized. The mutant p53 extended the life-span of the cells but could not immortalize them. However, the cells into which the p53 had been introduced were immortalized with 4NQO or x-rays. The identical treatment of the cells with these agents did not make the cells immortal. These results demonstrate that p53 can play a role in aging/immortalization of human cells.
Our other experiments showed downregulation of SdiI and enhanced expression of cdc2, cdk4, and myc in the immortalized cell lines. These results indicate that cellular aging/immortalization is controlled by both negatively and positively regulating genes related to cell growth.
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