| Project/Area Number |
20592329
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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 |
Surgical dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUOKA Yudai Osaka University, 大学院・歯学研究科, 招聘教員 (50448148)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHARA Hirokazu 大阪大学, 大学院・歯学研究科, 招聘教員 (70324796)
KOGO Mikihiko 大阪大学, 大学院・歯学研究科, 教授 (20205371)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 口腔外科学一般 / 口腔扁平上皮癌 / アポトーシス / 低分子Gたんばく質 / Rac / 低分子Gたんぱく質 |
|---|
| Research Abstract |
Among Rho family members, Rac has been implicated in the regulation of cell survival and apoptosis. However, the mechanisms underlying this process have not been fully elucidated. Here, we report that inhibition of Rac by a Rac-specific small molecule inhibitor, NSC23766, or transfection of dominant negative Rac (Rac-DN) elicits apoptosis in highly malignant oral squamous carcinoma cells (OSC-19 cells). Upon suppression of Rac, we observed up-regulation of c-Jun N-terminal kinase (JNK) and condensation of nuclei, leading to caspase-dependent apoptosis. Pretreatment with a JNK-specific inhibitor, SP600125, decreased the effect of Rac inhibition on apoptosis, indicating that activation of JNK strongly correlates with apoptosis. Protein phosphatase 5 (PP5) has recently been reported as a downstream effector of Rac signaling. Stimulation of PP5 rescued apoptosis caused by Rac inhibition by dephosphorylating JNK. These results demonstrate that inhibition of Rac activity leads to the suppression of PP5 activity, which results in extensive activation of JNK and caspase-dependent apoptosis. Taken together, Rac inhibition may represent a novel therapeutic approach for oral squamous carcinoma.
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