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Understanding heterogeneity within cell population in the process of acquiring anti-cancer drug resistance

Research Project

Project/Area Number 17K18359
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
System genome science
Research InstitutionToho University (2019)
Osaka University (2017-2018)

Principal Investigator

MAGI Shigeyuki  東邦大学, 医学部, 助教 (90708546)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords乳がん / 薬剤耐性 / 1細胞解析 / 一細胞解析 / がん / がん細胞の特性 / モデル化とシミュレーション
Outline of Final Research Achievements

In order elucidate the biological significance of heterogeneity within the cell population in the process of breast cancer cells acquiring tamoxifen resistance, the author examined cell growth assay and single cell gene expression analysis with MCF-7 breast cancer cells, that were continuously treated with tamoxifen. Cell growth stopped 3 to 6 weeks after administration of tamoxifen, but recovered again after 6 weeks and acquired resistance. A result of single cell gene expression analysis implied that the heterogeneity within cell population increased due to initial response, then decreased due to cell selection, and finally re-increased due to accumulation of genetic mutations. The author revealed that there exist several trajectories toward to two major subpopulations of resistant cells with different characteristics in the background of the heterogeneity.

Academic Significance and Societal Importance of the Research Achievements

従来の薬剤耐性研究においては、実験手法や結果の解釈の容易さから、野生型株と耐性株を比較する研究手法が主流であった。本研究の成果は、従来型研究で見過ごされてきた耐性獲得の途中過程を経時評価することにより、耐性獲得に伴う不均一性の変化、およびその裏側にある細胞亜集団の複数の出現軌跡を見出した点である。この成果は、複数の軌跡を同時に遮断することで耐性細胞の出現を抑制する新たな治療法の確立につながり、学術的にも社会的にも大きな意義を持つと思われる。

Report

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

    (20 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Presentation (18 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results)

  • [Int'l Joint Research] Universidad Nacional Autonoma de Mexico(メキシコ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University College Dublin(アイルランド)

    • Related Report
      2019 Annual Research Report
  • [Presentation] A comprehensive model of heterogeneous cell cycle responses2019

    • Author(s)
      Imoto H, Ebata K, Magi S, Zhang S, Okada M
    • Organizer
      The 57th Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 時系列・一細胞解析による抗がん剤耐性獲得過程の理解2019

    • Author(s)
      間木重行, 奇 世媛, 鵜飼正雄, 鈴木 穣, 岡田眞里子
    • Organizer
      日本バイオインフォマティクス学会 2019年年会・ 第8回生命医薬情報学連合大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 時系列・一細胞解析による抗がん剤耐性獲得過程の理解2019

    • Author(s)
      間木 重行
    • Organizer
      新学術領域研究「数理シグナル」 第3回 若手ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] 時系列・一細胞解析から見える抗がん剤耐性獲得過程2019

    • Author(s)
      間木 重行
    • Organizer
      大阪大学蛋白質研究所セミナー 「がん研究の新機軸」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] オートファジーが関与する抗がん剤耐性獲得過程の数理モデル解析2019

    • Author(s)
      間木 重行
    • Organizer
      令和元年 「数理シグナル」 領域推進会議
    • Related Report
      2019 Annual Research Report
  • [Presentation] Model-based identification of ErbB network principles among cell types2019

    • Author(s)
      Imoto H, Ebata K, Zhang S, Magi S, Okada M
    • Organizer
      The 20th International Conference of Systems Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A NF-κB - p38 MAPK crosstalk shapes oscillatory gene expression2019

    • Author(s)
      Michida H, Ando M, Magi S, Okada M
    • Organizer
      The 20th International Conference of Systems Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A hybrid mathematical model for design and optimization of tamoxifen treatment in MCF-7 breast cancer cells2019

    • Author(s)
      Dominguez-Huttinger E, Magi S, AntoniA A, Ortiz O., Ramirez A.R., Okada M
    • Organizer
      The 20th International Conference on Systems Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crosstalk between the estrogen receptor and ErbB signaling pathways in breast cancer cells2019

    • Author(s)
      Zhang S, Magi S, Okada M
    • Organizer
      the 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Understanding negative feedback mechanism of ErbB signaling using mathematical modeling of cell population dynamics2018

    • Author(s)
      Shigeyuki Magi
    • Organizer
      Frontiers of Multiscale Structural Biology: Order-disorder transitions and dynamic membrane interactions
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 乳がん細胞におけるタモキシフェン耐性獲得過程の時系列解析2018

    • Author(s)
      間木重行
    • Organizer
      大阪大学大学院医学系研究科 第11回 若手研究フォーラム
    • Related Report
      2018 Research-status Report
  • [Presentation] Time-series analysis on the process of acquiring tamoxifen resistance in breast cancer cells2018

    • Author(s)
      Shigeyuki Magi, Yutaka Suzuki, Mariko Okada
    • Organizer
      日本癌学会 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 乳がん細胞におけるタモキシフェン耐性獲得過程の時系列解析2018

    • Author(s)
      間木重行
    • Organizer
      新学術領域「代謝統合オミクス」第一回若手合宿
    • Related Report
      2018 Research-status Report
  • [Presentation] Time-series analysis on the process of acquiring tamoxifen resistance in breast cancer cells2018

    • Author(s)
      Shigeyuki Magi, Sewon Ki, Masao Ukai, Yutaka Suzuki, Mariko Okada
    • Organizer
      日本分子生物学会 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Time‐Series Analysis on the Process of Acquiring Resistance for Estrogen Receptor Antagonist in Breast Cancer Cells2018

    • Author(s)
      Shigeyuki Magi
    • Organizer
      3rd Symposium on Complex Biodynamics + Networks
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳がん細胞におけるタモキシフェン耐性獲得過程の時系列解析2018

    • Author(s)
      間木重行
    • Organizer
      第一回がんと代謝研究会・若手の会
    • Related Report
      2017 Research-status Report
  • [Presentation] シグナルの定量解析と数理モデルによる分子制御機構の同定2017

    • Author(s)
      間木重行
    • Organizer
      生化学会近畿部会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 乳がんの内分泌療法抵抗正獲得過程の時系列解析2017

    • Author(s)
      間木重行 奇世媛 鵜飼正雄 鈴木穣 岡田眞里子
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report

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

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