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Modeling of cellular heterogeneity of drug resistance

Research Project

Project/Area Number 23650154
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bioinformatics/Life informatics
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

OKADA Mariko  独立行政法人理化学研究所, 細胞システムモデル化研究チーム, チームリーダー (10342833)

Co-Investigator(Kenkyū-buntansha) MITOSCH Karin  ドイツ財団フェロー
奇 世援  理化学研究所
湯本 範子  理化学研究所
Co-Investigator(Renkei-kenkyūsha) 岩本 一成  理化学研究所
木村 周平  鳥取大学
KHOLODENKO Boris  ダブリン大学
長嶋 剛史  東北大学
井上 聡  埼玉医科大学
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞不均一性 / シグナル伝達 / 乳がん / エストロゲン受容体 / 細胞ネットワーク / 数理モデル / 単一細胞計測
Research Abstract

In this study, we try to investigate heterogeneic cellular response in tamoxifen-treated breast cancer cell using experimental measurement and mathematical modeling. First, we measured phosphorylation or/and protein level of 35 mediators in signaling network related to estrogen receptor. We identified dysregulated activities in EGFR, ErbB2, ErbB3 receptor, estrogen receptor, GSK3beta, E2F1, CREB, Fos, Jun, JunB in averaged cell population. Furthermore, ErbB3, ERK and Akt showed cell-to-cell variation in their activities. We constructed mathematical model of this signaling network and investigate system properties of the network that may induce heterogeneic response.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (25 results)

All 2013 2012 2011

All Journal Article (14 results) (of which Peer Reviewed: 12 results) Presentation (11 results) (of which Invited: 3 results)

  • [Journal Article] Phase responses of oscillating components in a signaling pathway2013

    • Author(s)
      Nomura M, Okada-Hatakeyama M
    • Journal Title

      Front Physiol

      Volume: 2013;4 Pages: 68-68

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase responses of oscillating components in a signaling pathway.2013

    • Author(s)
      Nomura M, Okada-Hatakeyama M
    • Journal Title

      Front Physiol

      Volume: 4 Pages: 3389-3389

    • DOI

      10.3389/fphys.2013.00068

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells2012

    • Author(s)
      Hiroshima, M., Saeki, Y., Okada-Hatakeyama, M., and Sako, Y
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A.

      Volume: 109 (35) Pages: 13984-13989

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Catching transcriptional regulation by thermostatistical modeling2012

    • Author(s)
      Till D. F., Cheong, A., Okada-Hatakeyama, M., and Kholodenko, B.N
    • Journal Title

      Physical Biology

      Volume: 9(4) Pages: 45007-45007

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] An ErbB receptor-mediated AP-1 regulatory network is modulated by STAT3 and c-MYC during calcium-dependent keratinocyte differentiation2012

    • Author(s)
      Saeki Y., Nagashima T., Kimura S., and Okada-Hatakeyama M
    • Journal Title

      Exp. Dermatol

      Volume: 21(4) Pages: 293-298

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inference of S-system models of genetic networks by solving one-dimensional function optimization problems2012

    • Author(s)
      Kimura S., Araki D., Matsumura K., and Okada-Hatakeyama M
    • Journal Title

      Math. Biosci

      Volume: 235(2) Pages: 161-170

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] がん細胞情報伝達のダイナミクスとシステムバイオロジー2012

    • Author(s)
      岡田眞里子
    • Journal Title

      応用数理

      Volume: 22 (3)

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Journal Article] Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells.2012

    • Author(s)
      Hiroshima, M., Saeki, Y., Okada-Hatakeyama, M., and Sako, Y.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A.

      Volume: 109 Issue: 35 Pages: 13984-13989

    • DOI

      10.1073/pnas.1200464109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catching transcriptional regulation by thermostatistical modeling.2012

    • Author(s)
      Till D. F., Cheong, A., Okada-Hatakeyama, M., and Kholodenko, B.N.
    • Journal Title

      Physical Biology

      Volume: 9 Issue: 4 Pages: 45007-45007

    • DOI

      10.1088/1478-3975/9/4/045007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An ErbB receptor-mediated AP-1 regulatory network is modulated by STAT3 and c-MYC during calcium-dependent keratinocyte differentiation.2012

    • Author(s)
      Saeki Y., Nagashima T., Kimura S., and Okada-Hatakeyama M.
    • Journal Title

      Exp. Dermatol.

      Volume: 21 Issue: 4 Pages: 293-298

    • DOI

      10.1111/j.1600-0625.2012.01453.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] nference of S-system models of genetic networks by solving one-dimensional function optimization problems.2012

    • Author(s)
      Kimura S., Araki D., Matsumura K., and Okada-Hatakeyama M.
    • Journal Title

      Math. Biosci

      Volume: 235 Issue: 2 Pages: 161-170

    • DOI

      10.1016/j.mbs.2011.11.008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A rank-based statistical test for measuring synergistic effects between two gene sets2011

    • Author(s)
      Shiraishi Y., Okada-Hatakeyama M., and Miyano S
    • Journal Title

      Bioinformatics

      Volume: 27(17) Pages: 2399-2405

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A kinetic model explains increased gefitinib sensitivity associated with Mig6 expression2011

    • Author(s)
      Naruo, Y., Nagashima, T., Ushikoshi-Nakayama, R., Saeki, Y., Nakakuki, T., Naka, T., Tanaka, H., Tsai, S-F., and Okada-Hatakeyama, M
    • Journal Title

      BMC Systems Biology

      Volume: 5(1) Pages: 29-29

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子ネットワークのスイッチが細胞運命を決定する2011

    • Author(s)
      岡田眞里子
    • Journal Title

      実験医学増刊

      Volume: 29 (12) Pages: 127-132

    • Related Report
      2012 Final Research Report
  • [Presentation] A switch in NF-kappa B signaling2013

    • Author(s)
      Mariko Okada
    • Organizer
      The first annual Winter q-Bio Meeting
    • Place of Presentation
      Hawaii, USA (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] A switch in NF-kappa B signaling.2013

    • Author(s)
      Mariko Okada
    • Organizer
      The first annual Winter q-Bio Meeting
    • Place of Presentation
      Hawaii, USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] シグナル転写ネットワークのダイナミクスと疾病制御2012

    • Author(s)
      岡田眞里子
    • Organizer
      文部科学省イノベーションシステム整備事業 先端融合領域イノベーション創出拠点形成プログラム「翻訳後修飾プロテオミクス医療研究拠点の形成」第4回公開シンポジウム バイオインフォマティクスの最前線
    • Place of Presentation
      横浜 (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] 実験と計算による細胞情報処理機構の同定2012

    • Author(s)
      岡田眞里子
    • Organizer
      情報処理学会 バイオ情報学研究会 (SIG BIO)
    • Place of Presentation
      飯塚 (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] シグナル転写ネットワークのダイナミクスと疾病制御.2012

    • Author(s)
      岡田眞里子
    • Organizer
      文部科学省イノベーションシステム整備事業 先端融合領域イノベーション創出拠点形成プログラム「翻訳後修飾プロテオミクス医療研究拠点の形成」第4回公開シンポジウム バイオインフォマティクスの最前線
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 実験と計算による細胞情報処理機構の同定.2012

    • Author(s)
      岡田眞里子
    • Organizer
      情報処理学会 バイオ情報学研究会 (SIG BIO)
    • Place of Presentation
      飯塚
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Identifying logics of signal-transcription network for cellular differentiation2011

    • Author(s)
      Mariko Okada
    • Organizer
      IFReC / IPR Joint Seminar
    • Place of Presentation
      Osaka (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] Transcriptional feedback shapes signaling activity in cancer2011

    • Author(s)
      Mariko Oakda
    • Organizer
      JCR-AACR Joint Symposium
    • Place of Presentation
      Nagoya (招待発表,国内学会・研究会)
    • Related Report
      2012 Final Research Report
  • [Presentation] 細胞運命を決定する遺伝子ネットワークのスイッチ機構2011

    • Author(s)
      岡田眞里子
    • Organizer
      ミニシンポジウム : 計算ウイルス学・免疫学の展開
    • Place of Presentation
      京都 (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] c-Fos転写因子のスイッチ様活性化を説明するシグナル?転写ネットワークの速度論的解析2011

    • Author(s)
      岡田眞里子
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都 (招待発表)
    • Related Report
      2012 Final Research Report
  • [Presentation] シグナル伝達の空間制御と不均一性に関するモデル化の試み2011

    • Author(s)
      岡田眞里子
    • Organizer
      理研シンポジウム「細胞システムの動態と論理III」
    • Place of Presentation
      和光 (招待発表)
    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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