2017 Fiscal Year Final Research Report
Seeking a novel therapy for hereditary breast cancer by modulating alternative splicing
| Project/Area Number |
15K10050
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Fukuoka University (2016-2017)
Kyoto University (2015) |
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Principal Investigator |
Ohe Kenji 福岡大学, 薬学部, 准教授 (30419527)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | スプライシング |
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| Outline of Final Research Achievements |
Hereditary breast cancer caused by the BRCA1 mutation 5382insC is due to a one base pair insertion in exon 20 and results in a frame shift. In order to correct this, we tried various ways to skip exon 20, eventually which corrects the frameshift.We tried small splice modifying compounds,antisense RNA, modified U1 snRNA, and modified U7 snRMA, but all ended up in a failure. However, when we evaluated BRCA1 protein (C term Ab)by Western blot, we found TG003 increased the corrected in-frame BRCA1 protein accompanying decreased cell viability of HCC1937 cells which harbor the BRCA1 5382insC mutation endogenously.Exon skipping may have been induced in other exons besides exon 20 by TG003, which we are still persuing.
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| Free Research Field |
スプライシング
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