| Project/Area Number |
12670130
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUJIMOTO Jiro Insitute of Medical Science, The University of Tokyo, Research Associate, 医科学研究所, 助手 (60282521)
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| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cell cycle / protein kinase / tumor-supressor genes / 細胞周期 |
|---|
| Research Abstract |
The LATS1 and LATS2 genes are mammalian homologs of the Drosophila LATS (large tumor suppressor) gene that encodes a serine/threonine kinase. Although LATS2 is expressed in various human cancer cell lines, we identified some kidney tumor cell lines that do not express LATS2. Both LATS1 and Bcl-2 are highly phosphorylated in LATS2-positive but not in LATS2-deficient, paclitaxel-treated cells.
In addition, LATS2-deficient cells are less sensitive to paclitaxel-induced apoptosis. Ectopic expression of LATS2 in LATS2-deficient cells restores paclitaxel sensitivity , resulting in the phosphorylation of LATS1 and Bcl-2, and the induction of apoptosis. These observations indicate that LATS2 is involved in M-phase progression through the control of LATS1 and Bcl-2 phosphorylation, thereby regulating cellular entry into apoptosis and suggest that the status of LATS kinase genes in clinical tumors may define their sensitivity to paclitaxel-mediated chemotherapy.
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