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Establishment of transgenic HRAS medaka as a tumor model for in vivo drug screening

Research Project

Project/Area Number 24591633
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

MATSUZAKI Yuriko  慶應義塾大学, 医学部, 助教 (40255435)

Co-Investigator(Renkei-kenkyūsha) SAYA Hideyuki  慶應義塾大学, 医学部, 教授 (80264282)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsがん遺伝子導入メダカ / 抗癌剤スクリーニング / メダカ腫瘍モデル / HRAS / HRAS高発現 / トランスジェニックメダカ / メダカ / トランスジェニック / RAS / 薬剤スクリーニング
Outline of Final Research Achievements

We have previously reported a transgenic medaka strain expressing human HRAS mutant gene. Here, we further intend to establish a novel drug screening system using this medaka. In the first screen using our drug library, we obtained 35 drugs which could decrease pigmentation of zebrafish embryos. Seven out of 35 drugs were selected as candidate drugs because they had affected the downregulation of the gene for marker of embryonic neural crest progenitors. Before the second screening, we tried to validate the experimental system using the transgenic HRAS medaka. Inhibitors for downstream molecules of RAS signaling were administered to the HRAS medaka. Treatment with sorafenib, an inhibitor of Raf kinase, improved their survival, and Trametinib, an inhibitor of MEK, decreased the levels of phosphorylated ERK in the tumor tissue. The in vivo system presented here is promising to screen potential anticancer drugs.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (6 results) Remarks (3 results)

  • [Journal Article] Establishment of HRASG12V Transgenic Medaka as a Stable Tumor Model for In Vivo Screening of Anticancer Drugs.2013

    • Author(s)
      Matsuzaki Y, Hosokai H, Mizuguchi Y, Fukamachi S, Shimizu A, Saya H
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 1 Pages: e54424-e54424

    • DOI

      10.1371/journal.pone.0054424

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 松崎ゆり子・佐谷秀行他2014

    • Author(s)
      Transcription activator-like effector nucleases (TALENs)システムを用いて作製したphosphatase and tensin homolog (PTEN)ノックアウトメダカ
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神奈川・パシフィコ横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬剤スクリーニングに用いる癌遺伝子HRAS導入メダカモデルの確立2014

    • Author(s)
      松崎ゆり子・佐谷秀行
    • Organizer
      日本癌学会
    • Place of Presentation
      神奈川・パシフィコ横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Establishment of transgenic HRAS medaka as a tumor model for in vivo drug screening2014

    • Author(s)
      松崎ゆり子・佐谷秀行他
    • Organizer
      小型魚類研究会
    • Place of Presentation
      慶應義塾大学薬学部
    • Year and Date
      2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Establishment of transgenic medaka as a stable tumor model for in vivo screening of anticancer drugs

    • Author(s)
      松崎ゆり子・細貝春・水口幸代・清水厚志・佐谷秀行
    • Organizer
      アメリカ癌学会
    • Place of Presentation
      米国・ワシントンDC
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗癌剤スクリーニングに用いるための遺伝子導入メダカ腫瘍モデルの確立

    • Author(s)
      松崎ゆり子・佐谷秀行
    • Organizer
      日本動物学会
    • Place of Presentation
      岡山県岡山市
    • Related Report
      2013 Research-status Report
  • [Presentation] Establishment of the medaka melanoma model and drug administration trials

    • Author(s)
      Hosokai H, Shimizu A, Saya H, Fukamachi S, Mizuguchi Y, Matsuzaki Y
    • Organizer
      第18回小型魚類研究会
    • Place of Presentation
      京都大学(京都)
    • Related Report
      2012 Research-status Report
  • [Remarks] メダカを用いた癌モデルの確立

    • URL

      http://www.genereg.jp/html/research/2012/07/post-3.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 慶應義塾大学医学部 先端医科学研究所遺伝子制御研究部門

    • URL

      http://genereg.jp/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 慶應義塾大学医学部先端医科学研究所遺伝子制御研究部門

    • URL

      http://genereg.jp/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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