| Project/Area Number |
24501361
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
EGUTI Ryoji 兵庫医科大学, 医学部, 助教 (00461088)
KUBO Syuji 兵庫医科大学, 医学部, 准教授 (10441320)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Srcファミリーキナーゼ / 中皮腫 / アポトーシス / Fyn / Lyn / スフェロイド / ダサチニブ |
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| Outline of Final Research Achievements |
Malignant mesothelioma is an aggressive tumor arising from mesothelial cells of serous membranes. We examined the role of Src family kinases (SFKs) in mesothelioma cells. We found that PP2, a selective SFK inhibitor, inhibited SFK activity and induced apoptosis mediated by caspase-8 in NCI-H28. Src, Yes, Fyn and Lyn protein, which are members of the SFK, were expressed in mesothelioma cell lines, while NCI-H28 cells were deficient in Fyn protein. PP2 reduced Lyn protein levels and suppressed SFK activity. Lyn siRNA induced apoptosis in Fyn-deficient NCI-H28 cells. Double RNAi knockdown of Fyn and Lyn induced apoptosis in Fyn-expressing NCI-H2052 and ACC-MESO-4 cells. Present study suggests that SFK inhibitors induce caspase-8-dependent apoptosis caused by reduction of Lyn protein in Fyn-deficient mesothelioma cells. This provides a new insight for treatment of mesothelioma by simultaneous inhibition of Fyn and Lyn.
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