| Project/Area Number |
16K20047
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Aichi Cancer Center Research Institute (2018)
Nagoya University (2016-2017) |
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Principal Investigator |
HAMADA Shunsuke 愛知県がんセンター(研究所), がん病態生理学分野, 研究員 (90747289)
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| Research Collaborator |
NISHIDA Yoshihiro
SAKAI Tomohisa
KOIKE Hiroshi
TSUKUSHI Satoshi
YOSHIDA Masahiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | デスモイド型線維腫症 / β-catenin / CTNNB1遺伝子 / 遺伝子変異 / Wntシグナル / WNT/β-catenin系シグナル / βカテニン / プロテオーム / 医療・福祉 / シグナル伝達 / デスモイド腫瘍 |
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| Outline of Final Research Achievements |
We investigated the molecular biological differences and their significance of each CTNNB1 gene mutation variant that could be a therapeutic predictive marker of desmoid-type fibromatosis. The differences in nuclear β-catenin accumulation and expression status of downstream genes were observed for each mutation variant, and S45F mutated cells generally tended to have a more pronounced enhancement of WNT / β-catenin signaling. We presented these results at the academic meeting and published a paper on the difference in nuclear accumulation of β-catenin among each mutation variant. Protein microarray was performed to evaluate protein expression, and its result showed that specific gene mutation promoted the protein expression of TGF-β and EGFR.
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| Academic Significance and Societal Importance of the Research Achievements |
デスモイド型線維腫症のCTNNB1遺伝子変異型は臨床的に術後再発率や薬物治療効果に影響を与えることが報告されており実際に本邦における治療アルゴリズムでも取り入れられている。本研究結果より変異型の相違が何らかの形で主にWNT/β-catenin系シグナル発現亢進を通し下流の蛋白発現に相違を及ぼしていることが示唆され、最終的に再発や薬物治療抵抗性といった臨床的予後の相違に関与していると考えられた。今後より厳密な治療マーカーとしての確立化や新たな治療標的薬の開発につながることが期待される。
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