2013 Fiscal Year Final Research Report
Combination of splicing factor inhibitor and histone deacetylase inhibitor
| Project/Area Number |
23591975
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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 |
Digestive surgery
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMANO Tomoki 兵庫医科大学, 医学部, 講師 (00599318)
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| Project Period (FY) |
2011 – 2013
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| Keywords | スプライシング因子 / 阻害剤 / 遺伝子変異 |
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| Research Abstract |
SF3B1 gene mutations and their relevance to cancer progression have been shown in hematological malignancies and melanoma. We assessed the significance of inhibition of SF3B1 gene expression and SF3B1 gene mutation in colorectal cancer (CRC) using FR901464 (FR), a specific inhibitor of SF3B1. FR showed strong cytotoxicity in CRC cancer cell lines. All FR-resistant clones had the missense mutations in the codon 1074, which mutations have not been found in 245 CRC patients. Animal experiments showed antitumor effect by FR was limited by toxicity, although FR resistant clones with SF3B1 mutations grew significantly slowly than their parental cells. Microarray analysis showed FR inhibited pathways related with cell cycle, Fanconi anemia, homologous recombination, nucleotide excision repair. The influence of SF3B1 mutation of codon 1074 on alternative splicing has not been found like uveal melanoma. These results indicate that SF3B1 is a novel molecular target for CRC treatment.
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Research Products
(6 results)
