| Project/Area Number |
09680711
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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 |
Cell biology
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| Research Institution | Chiba University |
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Principal Investigator |
HIWASA Takaki Chiba University, School of Medicine, Lecturer, 医学部, 講師 (30260251)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWARA Akira Chiba Cancer Canter Research Institute, Division of Biochemistry, Head, 生化学研究部, 部長 (50117181)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Apoptosis / Protease / Caspase / Cancer / Ras / がん抑制活性 |
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| Research Abstract |
Although it is generally accepted that caspase family proteases play central roles in induction of apoptosis, their other biological activity remains to be proved. Therefore, we have transfected cDNAs of caspase-1 (ICE), 2 (ICH-1) and 3 (CPP32) into Ha-ras-transformed NIH3T3 cells and investigated the effects after induction of their expression. High expression of these proteases alone did not result in apoptosis-like cell death. However, morphological reversion was frequently observed in clones which overexpressed caspase-2. The reversion was well correlated to the expression level of caspase-2. Moreover, the reverted clones lost the ability of anchorage-independent growth in soft agar medium. These results suggest that caspase-2 possesses the tumor suppressive activity toward Ha-ras-transformed cells. Similar effects of caspase-2 were also observed for v-src-transformed NIH3T3 cells but not for Ki-ras-transformed cells. Thus, caspase-2 may affect a signal transduction pathway which is specific for Src and Ha-Ras. Further western blot analysis showed that the expression level of Ha-Ras was reduced in caspase-2-producing cells. In vitro incubation of cell extract of Ha-ras-transformed cells resulted in degradation of Ha-Ras protein. Th is degradation was completely suppressed in the presence of caspase inhibitors. Taken together, it is plausible that caspase-2 induced reversion of transformed cells by stimulating the degradation of Ha-Ras protein.
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