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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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | スプライシング因子 / 阻害剤 / 遺伝子変異 / SF３B1 / スプライシング |
|---|
| 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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Report
(4 results)
Research Products
(13 results)
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[Presentation] Low frequencies of SF3B1 mutations indicate SF3B1 inhibitor as a novel molecular targeted drug for colorectal cancer2013
Author(s)
Tomoki Yamano, Nagahide Matsubara ,Satoshi Tsuda, Hidenori Nakajima, Shuji Kubo, Mie Hamanaka, Masayoshi Kobayashi, Daisuke Yamagishi, Takashi Kuno, Kiyoshi Tsukamoto, Atsuko Tamamoto, Masafumi Noda, Naohiro Tomita
Organizer
2013米国癌学会
Place of Presentation
ワシントンDC（米国）
Related Report
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[Presentation] SF3B1 inhibitor as a novel molecular targeted drug candidate for colorectal cancer2013
Author(s)
Tomoki Yamano, Hidenori Nakajima, Shuji Kubo, Satoshi Tsuda, Mie Hamanaka, Masayoshi Kobayashi, Naohito Beppu, Daisuke Yamagishi, Kiyoshi Tsukamoto, Atsuko Tamamoto, Masafumi Noda, Nagahide Matsubara, Naohiro Tomita
Organizer
第72回日本癌学会
Place of Presentation
横浜
Related Report
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