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Development of retrotransposon gene PEG10 targeting treatment for neuroendocrine prostate cancer

Research Project

Project/Area Number 17K11133
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKyoto University

Principal Investigator

Shusuke Akamatsu  京都大学, 医学研究科, 助教 (20767248)

Co-Investigator(Kenkyū-buntansha) 山崎 俊成  京都大学, 医学研究科, 講師 (00607749)
井上 貴博  京都大学, 医学研究科, 准教授 (80511881)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords神経内分泌前立腺癌 / PEG10 / PDX / 細胞株 / 前立腺癌 / 神経内分泌癌 / レトロトランスポゾン遺伝子
Outline of Final Research Achievements

PEG10 is a unique particle derived from retrotransposon and promotes growth and invasion of neuroendocrine prostate cancer (NEPC). At first, we aimed to elucidate the mechanism of tumor proliferation focused on the particle interacting with PEG10, but enough achievements were not obtained. Next, we tried to culture xenograft model and cell line derived from a NEPC patient. We succeeded in establishing a new NEPC model named KUCaP13. We confirmed that the model was derived from prostate cancer and that it had features of NEPC. Furthermore, we generated the PEG10 knockdown (shPEG10) strain and evaluated its proliferation in vivo. The growth of shPEG10 was suppressed clearly, and this result suggested that PEG10 could be a therapeutic target.

Academic Significance and Societal Importance of the Research Achievements

本研究ではPEG10を標的とした具体的な治療法開発までは到達できなかったが、NEPC患者由来の新規実験モデルが樹立できた。前立腺癌治療中に発生したNEPCであり、近年AR標的薬の増加に伴い増えているNEPCを反映する非常に有用な実験モデルである。このような特徴を有する細胞株の樹立は今までになく、KUCaP13は治療探索において貴重な細胞株と言える。
今回作成されたKUCaP13のNEPC細胞株を使って改めてPEG10が治療標的となりうると確認できたことは大きな前進であり、今後この細胞株を利用した様々な実験系が想定され、新規治療開発への手掛かりとなることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (1 results)

  • [Journal Article] PEG10 is associated with treatment-induced neuroendocrine prostate cancer2019

    • Author(s)
      Kim Soojin、Thaper Daksh、Bidnur Samir、Toren Paul、Akamatsu Shusuke、Bishop Jennifer L、Colins Colin、Vahid Sepideh、Zoubeidi Amina
    • Journal Title

      Journal of Molecular Endocrinology

      Volume: 63 Issue: 1 Pages: 39-49

    • DOI

      10.1530/jme-18-0226

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical and molecular features of treatment-related neuroendocrine prostate cancer2018

    • Author(s)
      Akamatsu Shusuke、Inoue Takahiro、Ogawa Osamu、Gleave Martin E
    • Journal Title

      International Journal of Urology

      Volume: 25 Issue: 4 Pages: 345-351

    • DOI

      10.1111/iju.13526

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The retrotransposon-derived gene PEG10 directly binds with WWP2 and affects PTEN protein degradation in prostate cancer.2017

    • Author(s)
      岡所 広祐、赤松 秀輔、川井 禎久、水野 桂、李 新、住吉 崇幸、牧野 雄樹、後藤 崇之、小林 恭、井上 貴博、小川 修
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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