| Project/Area Number |
15K15473
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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 |
General surgery
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| Research Institution | Kansai Medical University (2016)
Kyoto University (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 間葉転換解除 / トリプルネガティブ乳癌 / 膠芽腫 / EMT / MET / miR-200 |
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| Outline of Final Research Achievements |
Through the shRNA library screening with MET reporter, I identified two shRNAs, shP1 and shH1. The shP1-infected MDA-MB-231 (231) breast cancer cells became mammary progenitor-like cells, but not luminal, maintained proliferative ability, and hence exhibit sensitivity to paclitaxel and EGFR inhibition. On the other hand, the shP1-infected U251 glioblastoma (GBM) cells increased the expression of ES-like genes. In contrast to shP1-231 cells, the shP1-U251 cells showed marked inhibition of their proliferative ability both in vitro and in vivo. We have found the sequence shared between shP1 and shH1 corresponding to miR-200c sequence. The shH1 has stronger growth-suppressive effect than shP1 in both 231 and U251. We have also identified the target genes whose inhibition leads to marked suppression in growth in artificial cancer stem cell model. These genes also have miR-200 sequence in common. In the future plan, we will see the effect of miR-200- containing shRNAs of the genes.
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