| Project/Area Number |
21K16395
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | トリプルネガティブ乳癌 / 抗腫瘍免疫 / 高肺転移性細胞株4T1-LuM4.1 / 4T1-LUC / 早期再発診断マーカー / リキッドバイオプシー / AKT1 E17K変異 / PIK3CA H1047R変異 / PI3K/AKT経路 / 遺伝子変異 / 5ALA |
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| Outline of Research at the Start |
乳癌の中でもトリプルネガティブ乳癌（TN）症例は非TN症例よりも術後早期の再発が多く予後不良な経過をとる例があるため，早期再発診断マーカーや新規治療薬の研究が希求されている．
アミノレブリン酸（5ALA）の悪性腫瘍細胞の蛍光局在診断に着目，5ALA投与下血中循環腫瘍細胞（Circulating Tumor Cells，以下CTC）を検出し，5ALA蛍光強度と関連する遺伝子変異およびタンパク質の発現を検索することでCTCの高感度検出法の有用性について検討する．
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| Outline of Final Research Achievements |
A highly lung metastatic cell line 4T1-LuM4.1 was established by repeatedly transplanting the mouse triple-negative breast cancer cell line 4T1-LUC into mice, and 4T1-LuM4.1 was compared with 4T1-LUC by cell proliferation assay. It was revealed that the plant has high proliferative ability.
Additionally, through comprehensive gene analysis and RT-PCR, we identified four genes that were expressed more than 10 times higher in 4T1-LuM4.1 than in 4T1-LUC. Furthermore, it was confirmed by western blotting that the protein of the identified molecule was expressed in 4T1-LuM4.1.
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| Academic Significance and Societal Importance of the Research Achievements |
今後、肺転移性細胞株において有意に高発現する遺伝子と高肺転移性との関連について、抗腫瘍免疫応答の観点からの解明を試みる予定である。その成果は肺などに転移を来したトリプルネガティブ乳癌に対する新たな治療戦略の開発をする上で重要となる。
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