| Project/Area Number |
10680678
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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 | KURUME UNIVERSITY |
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Principal Investigator |
TSUNEOKA Makoto Kurume University, Institute of Life Science, Assistant professor, 分子生命科学研究所, 助教授 (50197745)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Myc / Ras / MEK / MAPK / Anchorage independent growth / tumorigenesis / apoptosis / RCCl / myc / 細胞増殖 / がん / N-myc / ras |
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| Research Abstract |
Although most types of cells require attachment to the substrate for proliferation, tumor cells do proliferate without attachment to the substrate, which is called as anchorage independent growth. Studies of tumorigenesis lead to understand anchorage independent growth, from which a new aspect for cell proliferation itself will emerge. Transformation of normal cells usually requires two or more cooperative oncogenic events. However, the mechanism of the oncogenic cooperation is unclear. The combination of c-myc and activated ras is the first pair of characterized genes to show oncogenic cooperation. First, in this project, I isolated cells transformed by myc and activated ras in which c-Myc expression is controllable (J. Biochem. 1998). Next. I isolated a transformed cell line in which activation of c-Myc and Ras are independently controllable (Oncogene 2000). Using these cells I show that after establishment of the transformed state by c-myc and activated ras, suppression of Ras/MEK signaling initiates apoptosis that is dependent on c-Myc activity. These results suggest that one of the conditions required for establishment of the u-;1ilSformeLl state is a block of apoptosis involving MEK activity. Suppression of apoptosis by MEK is not critical in general, but in cells transformed by c-myc plus a gene that activates the MAPK cascade it is necessary to avoid cell death. Furthermore I found that apoptosis regulation mechanism shown here include a novel regulatory mechanism for myc-dependent apoptosis.
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