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Development of treatment strategy targeting mechanisms mediated by TRIM family proteins

Research Project

Project/Area Number 20K08945
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionThe University of Tokyo (2021-2022)
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2020)

Principal Investigator

Azuma Kotaro  東京大学, 医学部附属病院, 講師 (30401110)

Co-Investigator(Kenkyū-buntansha) 井上 聡  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (40251251)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords乳がん / TRIM47 / TRIM25 / TRIM44 / TRIM39 / ユビキチン化 / スフェロイド培養 / 治療抵抗性 / TRIMファミリー / 三次元スフェロイド培養
Outline of Research at the Start

乳癌は日本人女性で最も起こりやすい癌であり、患者数や死亡者数は増加の一途を辿っている。乳癌による死亡者数増加の原因の一つとして、ホルモン療法が効きにくくなる現象やホルモン受容体がなくホルモン療法の対象とならない乳癌に対する有効な治療法が乏しいという点が挙げられる。申請者は、これまでの研究から、治療が効きにくい乳癌では、TRIM25およびTRIM47という2種類の蛋白質が増えていることを見出している。本研究では、これらの蛋白質の作用を解き明かし、患者さん由来の乳癌細胞の三次元培養という新たな手法を取り入れながら、これまでの問題点を克服できるような新たな乳癌治療法の開発を目指す。

Outline of Final Research Achievements

The purpose of this research is to discover new mechanisms of Tripatite Motif (TRIM) family proteins related to breast cancer promotion and resistance to therapies. We also aim to develop new therapeutic strategy for breast cancer. Through the entire research period, we are successful in elucidating clinical significance and new function of TRIM family proteins including TRIM25, TRIM39, TRIM44, and TRIM47. We published papers on all the four molecules during the research period. One of the mechanisms was the stabilization of interacting protein by ubiquitination. We are also establishing primary cancer cell lines from breast cancer patients which can be used for further preclinical studies to test the strategies targeting TRIM family-related mechanisms.

Academic Significance and Societal Importance of the Research Achievements

本研究においては、複数の乳癌の予後不良因子を蛋白質レベルで同定した。また、TRIM47の機能解析において、PKD3、PKC epsilonの安定化を介したメカニズムを示した点においても学術的な新規性を有する。さらに、ユビキチン分子のリジン27を介するポリユビキチン化という非典型的な分子修飾を示すことができた。本研究で同定した予後不良因子や関連蛋白質の知見を活用することにより、有効なオーダーメード医療を行う道が開け、現在の日本の乳癌の罹患率の高さや死亡数の増加傾向を鑑みると、社会的な意義も有しているといえる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Efp/TRIM25 and Its Related Protein, TRIM47, in Hormone-Dependent Cancers2022

    • Author(s)
      Azuma Kotaro、Inoue Satoshi
    • Journal Title

      Cells

      Volume: 11 Issue: 15 Pages: 2464-2464

    • DOI

      10.3390/cells11152464

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM47 activates NF-κB signaling via PKC-ε/PKD3 stabilization and contributes to endocrine therapy resistance in breast cancer2021

    • Author(s)
      Azuma Kotaro、Ikeda Kazuhiro、Suzuki Takashi、Aogi Kenjiro、Horie-Inoue Kuniko、Inoue Satoshi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 35

    • DOI

      10.1073/pnas.2100784118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] OCT1 Is a Poor Prognostic Factor for Breast Cancer Patients and Promotes Cell Proliferation via Inducing NCAPH2021

    • Author(s)
      Ogura Takuya、Azuma Kotaro、Sato Junichiro、Kinowaki Keiichi、Takayama Ken-Ichi、Takeiwa Toshihiko、Kawabata Hidetaka、Inoue Satoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 21 Pages: 11505-11505

    • DOI

      10.3390/ijms222111505

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM39 is a poor prognostic factor for patients with estrogen receptor‐positive breast cancer and promotes cell cycle progression2021

    • Author(s)
      Ogura Takuya、Azuma Kotaro、Takeiwa Toshihiko、Sato Junichiro、Kinowaki Keiichi、Ikeda Kazuhiro、Kawabata Hidetaka、Inoue Satoshi
    • Journal Title

      Pathology International

      Volume: 72 Issue: 2 Pages: 96-106

    • DOI

      10.1111/pin.13190

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined A20 and tripartite motif-containing 44 as poor prognostic factors for breast cancer patients of the Japanese population.2021

    • Author(s)
      Sato J, Azuma K, Kinowaki K, Ikeda J, Ogura T, Takazawa Y, Kawabata H, Kitagawa M, Inoue S.
    • Journal Title

      Pathol Int

      Volume: 71 Issue: 1 Pages: 60-69

    • DOI

      10.1111/pin.13047

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined use of immunoreactivities of RIG-I with Efp/TRIM25 for predicting prognosis of estrogen receptor-positive breast cancer patients.2021

    • Author(s)
      Sato J, Azuma K, Kinowaki K, Ikeda K, Ogura T, Takazawa Y, Kawabata H, Kitagawa M, Inoue S.
    • Journal Title

      Clin Breast Cancer

      Volume: - Issue: 5 Pages: 30328-1

    • DOI

      10.1016/j.clbc.2020.12.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] OCT1は乳がん患者の予後不良因子でありNCAPHを誘導し乳がん細胞の増殖を亢進する2022

    • Author(s)
      小倉拓也、東浩太郎、佐藤順一朗、木脇圭一、高山賢一、竹岩俊彦、川端英孝、井上聡
    • Organizer
      第30回 日本乳癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Prediction of endocrine resistance of breast cancer based on combined immunoreactivity study for TRIM47 and NR4A12022

    • Author(s)
      Kotaro Azuma, Kazuhiro Ikeda, Takashi Suzuki, Kuniko Horie, Satoshi Inoue
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Combined A20 and TRIM44 as poor prognostic factors for breast cancer patients of the Japanese population2021

    • Author(s)
      佐藤順一朗、東浩太郎、木脇圭一、池田和博、小倉拓也、髙澤豊、川端英孝、北川昌伸、 井上聡
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] TRIM47 contributes to tamoxifen resistance of breast cancer via stabilizing PKCepsilon2021

    • Author(s)
      Kotaro Azuma, Kazuhiro Ikeda, Takashi Suzuki, Kuniko Horie, Satoshi Inoue
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 乳がん内分泌療法に対する耐性予測因子TRIM47によるNF-κBシグナル活性化2021

    • Author(s)
      東浩太郎、池田和博、鈴木貴、堀江公仁子、井上聡
    • Organizer
      第93回日本内分泌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ER陽性乳癌におけるRetinoic acid-inducible gene IおよびA20発現の免疫組織化学解析2021

    • Author(s)
      佐藤順一朗、東浩太郎、木脇圭一、小倉拓也、池田和博、北川昌伸、川端英孝、井上聡
    • Organizer
      第28回日本乳癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Remarks] <プレスリリース>「ホルモン療法が効きにくい乳がんの原因を発見」

    • URL

      https://www.tmghig.jp/research/release/2021/0824.html

    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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