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Establishing the basis for new molecular-targeted therapies based on the signal transduction system by estrogen-related receptors for endometriosis

Research Project

Project/Area Number 18K09295
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kitawaki Jo  京都府立医科大学, 医学(系)研究科(研究院), 教授 (00204925)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords子宮内膜症 / エストロゲン関連受容体 / 分子標的治療 / イソフラボン
Outline of Final Research Achievements

Endometriosis grows and regresses in an estrogen-dependent manner. However, the classical estrogen receptor (ER)α-mediated signaling pathway is less dominant. The major pathway is that mediated via PGC-1α, a representative coactivator of estrogen-related receptor (ERR)α. In this study, we demonstrated that HX531, an antagonist of RXRα (one of the coactivators of PGC-1α), suppresses cell proliferation of endometriosis by inhibiting PGC-1α and suppressing the elevation of ERβ, IL-6 and IL-8, inflammatory cytokines, and survivin, an anti-apoptotic gene. Our findings suggest that the PGC-1α-mediated system is promising for establishing new therapeutic strategies.

Academic Significance and Societal Importance of the Research Achievements

従来、エストロゲン依存性増殖機構は古典的なERαを介するシグナル伝達経路によってのみ説明されてきたが、本研究では子宮内膜症においてPGC-1αを中心とした新たなエストロゲン依存性増殖機構を示した。
さらにこの系を阻害することによって子宮内膜症の細胞増殖が抑制されることを示した。現在まで子宮内膜症を完治させる治療法はなく、疼痛を緩和させるための内分泌療法が存在するのみであった。本研究成果は新たな治療戦略確立に有望であることが示された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 5 results)

  • [Journal Article] Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy2020

    • Author(s)
      Maeda Eiko、Koshiba Akemi、Mori Taisuke、Ito Fumitake、Kataoka Hisashi、Okimura Hiroyuki、Sugahara Takuya、Tarumi Yosuke、Kusuki Izumi、Khan Khaleque N.、Kitawaki Jo
    • Journal Title

      European Journal of Obstetrics & Gynecology and Reproductive Biology: X

      Volume: 7 Pages: 100108-100108

    • DOI

      10.1016/j.eurox.2020.100108

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic effect of the inhibitors of RAF/MEK and AXL on KRAS-mutated ovarian cancer cells with high AXL expression.2020

    • Author(s)
      Umemura S, Sowa Y, Iizumi Y, Kitawaki J, Sakai T.
    • Journal Title

      Cancer Sci.

      Volume: 111 Issue: 6 Pages: 2052-2061

    • DOI

      10.1111/cas.14414

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells.2019

    • Author(s)
      Kokabu T, Mori T, Matsushima H, Yoriki K, Kataoka H, Tarumi Y, Kitawaki J.
    • Journal Title

      Celler Oncology

      Volume: 42(2) Issue: 2 Pages: 223-235

    • DOI

      10.1007/s13402-019-00423-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer.2019

    • Author(s)
      Yoriki K, Mori T, Kokabu T, Matsushima H, Umemura S, Tarumi Y, Kitawaki J
    • Journal Title

      Scientific Reports

      Volume: 9(1) Issue: 1 Pages: 6697-6697

    • DOI

      10.1038/s41598-019-43261-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis.2019

    • Author(s)
      Akiyama K, Nishioka K, Khan KN, Tanaka Y, Mori T, Nakaya T, Kitawaki J.
    • Journal Title

      Am J Reprod Immunol

      Volume: 82 Issue: 2

    • DOI

      10.1111/aji.13147

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.2019

    • Author(s)
      Kataoka H, Mori T, Okimura H, Matsushima H, Ito F, Koshiba A, Tanaka Y, Akiyama K, Maeda E, Sugahara T, Tarumi Y, Kusuki I, Khan KN, Kitawaki J.
    • Journal Title

      Hum Reprod

      Volume: 34 Issue: 6 Pages: 1019-1029

    • DOI

      10.1093/humrep/dez067

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Equilin in conjugated equine estrogen increases monocyte-endothelial adhesion via NF-κB signaling2019

    • Author(s)
      Ito F, Mori T, Tarumi Y, Okimura H, Kataoka H, Tanaka Y, Koshiba A, Kitawaki J
    • Journal Title

      PLoS One

      Volume: 14 Issue: 1 Pages: 1-14

    • DOI

      10.1371/journal.pone.0211462

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis2018

    • Author(s)
      Takaoka O, Mori T, Ito F, Okimura H, Kataoka H, Tanaka Y, Koshiba A, Kusuki I, Shigehiro S, Amami T, Kitawaki J
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 181 Pages: 125-132

    • DOI

      10.1016/j.jsbmb.2018.04.004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy: A case report2018

    • Author(s)
      Okimura H, Tatsumi H, Ito F, Yamashita S, Kokabu T, Kitawaki J
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 44 Issue: 5 Pages: 972-977

    • DOI

      10.1111/jog.13595

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dienogest therapy during the early stages of recurrence of endometrioma might be an alternative therapeutic option to avoid repeat surgeries2018

    • Author(s)
      Koshiba A, Mori T, Okimura H, Akiyama K, Kataoka H, Takaoka O, Ito F, Matsushima H, Kusuki I, Kitawaki J
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 44 Issue: 10 Pages: 1970-1976

    • DOI

      10.1111/jog.13725

    • Related Report
      2018 Research-status Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2022-01-27  

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