| Project/Area Number |
15K06891
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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 |
Tumor therapeutics
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Migita Toshiro 公益財団法人がん研究会, がん化学療法センター 分子生物治療研究部, 研究員 (20462236)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | がん幹細胞 / 自己組織化 / 分化 / がん / 幹細胞 / がん化 |
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| Outline of Final Research Achievements |
c-myc is a driver oncogene of human liver cancer. We found that c-myc plays an important role in the maintenance of an undifferentiated state of liver cancer cell lines. c-myc depletion significantly inhibited the growth of liver cancer cells; however, it did not affect the level of alpha-fetoprotein (AFP), which is a marker of tumor malignancy.
ACTB, a gene encoding cytoskeletal beta-actin, is known as a target of cancer therapy. Inhibition of both c-myc and ACTB expression upregulated albumin expression, but downregulated AFP expression, suggesting the promotion of differentiation and the suppression of malignancy. Moreover, inhibition of both c-myc and ACTB expression strongly inhibited colony formation in 3D-culture compared to inhibition of c-myc alone, suggesting that inhibition of both c-myc and ACTB expression suppresses tumorigenicity.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞骨格遺伝子であるbeta-actinのがん細胞での役割については不明な点が多いが、正常細胞よりも量的に増加していることが多い。beta-actinとがん遺伝子であるc-mycを同時に抑制すると、分化促進と悪性度低下が見られたことより、がん細胞が機能的に正常化する可能性が示唆された。がん細胞特異的にbeta-actinの発現を抑制することができれば、beta-actinとc-mycの同時抑制は有望な治療法になると考えられた。
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