| Project/Area Number |
26640076
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA NORIOMI 京都大学, 医学研究科, 準教授 (20452336)
BABA TSUKASA 京都大学, 医学研究科, 講師 (60508240)
KONISHI IKUO 京都大学, 医学研究科, 教授 (90192062)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 癌幹細胞 / 化学療法耐性 / ヘッジホッグ経路 / 治療抵抗性獲得 / 卵巣癌 / SP分画 / 卵巣漿液性腺癌 / shRNA / single clonogeneisity / chemosennsitivity / sphere formation / shRNAライブラリー / ＳＰ分画 / single clonogenesity / chemosensitivity / sphere formation assay |
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| Outline of Final Research Achievements |
Ovarian cancer frequently acquires malignant phenotypes, such as chemo-resistance and tumorgenicity. We hypothesized that suppression of a gene’s expression might cause such an acquisition. We performed a functional genomics screen using a shRNA library targeting almost all genes. As a result, we found that suppression of only a single gene’s expression caused the acquisition of malignant phenotypes of ovarian cancer. In addition, we identified at least 6 such kinds of genes. Furthermore, suppression of those 6 genes enhanced malignant phenotypes of ovarian cancer via activation of the Hedgehog pathway. When we inhibited its pathway by a specific inhibitor, cyclopamine, it markedly decreased the malignant phenotypes which had been enhanced by suppression of each of 6 genes. Our findings should be helpful for developing the new treatment for refractory ovarian cancer.
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