| Project/Area Number |
20591947
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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 |
Obstetrics and gynecology
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| Research Institution | Kobe University |
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Principal Investigator |
SUDO Tamotsu Kobe University, 医学研究科, 医学研究員 (50397824)
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| Co-Investigator(Kenkyū-buntansha) |
IGUCHI Taisen 大学共同利用機関法人自然科学研究機構(共通施設), 岡崎統合バイオサイエンスセンター, 教授 (90128588)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | エストロゲン / p21 activated kinase-1 / VAV1 / ジエチルスチベストロール / ジエチルスチルベストロール |
|---|
| Research Abstract |
(1) PAK1, a major target of the small GTPases, growth factors and lipid signaling, regulates cell motility, hormone action, invasiveness, and survival, all of which are required for tumor development. We found phospho-PAK1 expression in 14% by immunohistochemical staining of ovarian cancer patients. Patients with phospho-PAK1 (+) in the tumor had poor survival compared with those with negative expression (P=0.02). Furthermore, PAK1 inhibition by PAK1 specific inhibitor (PAK18) greatly increased the sensitivity of phospho-PAK1 positive ovarian cancer cells to epirubicin.
(2) Vav1-positive tumors had a worse overall survival (P=0.0392) and progression free survival (P=0.0298) compared to Vav1-negative tumors in early-stage ovarian cancer patients. Significant down-regulation of E-cadherin was observed in SKOV-3-Vav1 versus control cells. Expression of VAV1 causally contributes to epithelial-mesenchymal transition and ovarian cancer progression through the suppression of E-cadherin.
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