| Project/Area Number |
18591828
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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 | Shinshu University |
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Principal Investigator |
HORIUCHI Akiko Shinshu University, Obstetrics and gynecology, Assistant Professor (80334895)
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| Co-Investigator(Kenkyū-buntansha) |
OSADA Ryousuke Shinshu University, Obstetrics and gynecology, Assistant Professor (80418722)
KONISHI Ikuo Kyoto University, Gynecology and Obstetrics, Professor (90192062)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hvnoxia / E-cadherin / Ovarian Cancer / invasion / 低酸素 / E-cadherin / HIF |
|---|
| Research Abstract |
Recent focusing attention is that the surrounding microenvironment plays in the process of tumorigenesis and tumor progression. We found that Hypoxia increased invasiveness of ovarian cancer cells via decreased E-cadherin expression. In this study, we investigate the mechanism of decreased E-cadherin expression under hypoxia.
Ovarian cancer cell lines were cultured under hypoxia, and the changes of E-cadherin expression was examined. In ovarian cancer cell (SKOV3), the expression of E-cadherin was decreased under hypoxic condition. In contrast, the expression of Snail, SIP1, and TWIST, E-cadherin transcriptional repressor, were increased under hypoxia. Luciferase assay showed that the transcriptional activity of Snail has increased under hypoxia by compared with under normal oxygen. Although both of siRNA for HIF-1α and HIF-2α inhibited the up-regulation of snail by hypoxia, the effect of HIF-1α was higher than that of HIF-2α. Additionally, the invasiveness of ovarian cancer cells was inhibited by HIF-1α siRNA.
These findings suggest that ovarian cancer cells were converted from epithelial character to mesenchymal character and increased invasiveness under hypoxia via upregulation of Snail.
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