2023 Fiscal Year Final Research Report
Development of innovative therapies for solid tumors by regulating plasticity
| Project/Area Number |
21K19568
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Nagoya University (2022-2023)
Kyoto University (2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐野 剛視 京都大学, 医学研究科, 助教 (60866309)
後藤 崇之 京都大学, 医学研究科, 講師 (90806605)
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Keywords | 可塑性 / 前立腺癌 / 神経内分泌前立腺癌 / 固形癌 / スクリーニング |
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| Outline of Final Research Achievements |
A reporter gene, AREluc was transduced into a novel neuroendocrine prostate cancer (NEPC) cell line, KUCaP13 cells to detect androgen receptor (AR) activity. Positive control cells (KUCaP13_AREluc_AR) overexpressing AR showed enhanced luminescence upon administration of synthetic androgen. We developed the screening system to detect AR re-expression in an NEPC cell line. Although a chemical screening of 1,552 known compounds revealed 30 candidate molecules potentially enhancing luciferase luminescence, all hit compounds were confirmed as false positives, probably due to their inhibitory activity on luciferase. We developed a screening system to evaluate the reversibility of plasticity using a novel NEPC cell line; however, no compound demonstrated the ability to regulate plasticity.
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| Free Research Field |
泌尿器癌
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| Academic Significance and Societal Importance of the Research Achievements |
神経内分泌前立腺癌(NEPC)においては系統的可塑性を反映した細胞株が存在せず、大規模なスクリーニングは困難であった。我々は系統的可塑性の表現型を有する新規NEPC細胞株KUCaP13を樹立し、これを用いて可塑性の可逆性を評価できるスクリーニング系を開発した。本研究では単一化合物ではアンドロゲンレセプター(AR)を再発現できなかったが、複数の化合物を組み合わせるなど、今後さらなる研究に応用可能である。また前立腺癌は他の固形癌と異なりAR活性で可塑性を評価できるので、他の固形癌では困難な可塑性を評価するスクリーニング系で得られた成果は、他の癌種における可塑性研究への応用が期待できる。
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