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Investigation of therapeutic targets against endocrine-resistant breast cancer cells

Research Project

Project/Area Number 21K08670
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 InstitutionHiroshima University

Principal Investigator

Takahashi Ryou-u  広島大学, 医系科学研究科(薬), 准教授 (10625510)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords乳がん / 非翻訳型RNA / 薬剤耐性 / ホルモン療法 / タモキシフェン耐性 / がん微小環境 / ホルモン受容体
Outline of Research at the Start

非翻訳型RNAであるmicroRNA-27b(miR-27b)の発現を指標として「エストロゲン(ER)受容体の発現が低下した細胞集団」の性状解析を行い、タモキシフェン耐性が獲得される過程においてどのような役割を担うのかを明らかにする。また、性状解析から得られた遺伝子発現プロファイルをもとにER受容体陰性細胞における増殖メカニズムを検討し、新規治療標的分子の同定を試みる。同定した標的遺伝子をsiRNAなどの核酸や低分子化合物により抑制可能かどうかも検討する。これにより、ホルモン療法耐性の乳がん症例に対する新たな治療基盤を構築する。

Outline of Final Research Achievements

We previously reported that down-regulation of microRNA-27b (miR-27b) induced the docetaxel resistance in estrogen receptor (ER)-positive breast cancer. After these findings, we found that miR-27b was down-regulated in endocrine-resistant breast cancer cells. In this study, we aimed to analyze the characteristics of endocrine-resistant breast cancer cells via evaluating miR-27b expression. We found that ER was down-regulated in miR-27b down-regulated cells. We also observed the elevated expression of CEACAM6 in miR-27b down-regulated cells. Therefore, our current study identified CEACAM6 as a novel marker for hormone therapy-resistant breast cancer cells.

Academic Significance and Societal Importance of the Research Achievements

ER陽性のルミナルタイプの乳がんは乳がん症例の約7割を占める。ルミナル症例の約2割ではホルモン療法に耐性が見られ再発の可能性が高い。本研究では、ルミナル症例が予後不良となる一因としてERの発現低下などのルミナル形質の喪失される可能性を示した。また、ERの発現低下した細胞においてCEACAM6の発現が亢進することも明らかにした。以上の成果から、本研究はルミナル症例においてホルモン療法の奏効性を予測できる新規マーカーとしてCEACAM6が有用である可能性を示した。また、CEACAM6陽性乳がん細胞を対象とした治療標的分子を同定することで難治性のルミナル症例の予後不良を改善できることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021 Other

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 3 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches2024

    • Author(s)
      Welsh, J. A., Goberdhan, D. C. I., O’Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrugger, U., Falcon-Perez, J. M., Fu, Q.-L., Hill, A. F., Lenassi, M., Lim, S. K., Mahoney, M. G., Mohanty,.. .Kumagai, Y.,... Witwer, K. W
    • Journal Title

      Journal of Extracellular Vesicles

      Volume: 13 Issue: 2

    • DOI

      10.1002/jev2.12404

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Downregulation of Histone H3.3 Induces p53-Dependent Cellular Senescence in Human Diploid Fibroblasts2024

    • Author(s)
      Yamamoto Yuki、Takahashi Ryou-u、Kinehara Masaki、Yano Kimiyoshi、Kuramoto Tatsuya、Shimamoto Akira、Tahara Hidetoshi
    • Journal Title

      Genes

      Volume: 15 Issue: 5 Pages: 543-543

    • DOI

      10.3390/genes15050543

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association Between Telomere G-Tail Length and Coronary Artery Disease or Statin Treatment in Patients With Cardiovascular Risks ― A Cross-Sectional Study ―2023

    • Author(s)
      Nose Daisuke、Shiga Yuhei、Takahashi Ryou-u、Yamamoto Yuki、Suematsu Yasunori、Kuwano Takashi、Sugihara Makoto、Kanda Miyuki、Tahara Hidetoshi、Miura Shin-ichiro
    • Journal Title

      Circulation Reports

      Volume: 5 Issue: 8 Pages: 338-347

    • DOI

      10.1253/circrep.CR-23-0038

    • ISSN
      2434-0790
    • Year and Date
      2023-08-10
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leukocyte Telomeric G-Tail Length Shortening Is Associated with Esophageal Cancer Recurrence2022

    • Author(s)
      Han Jiayan、Hayashi Soichiro、Takahashi Ryou-u、Hirohata Ryosuke、Kurokawa Tomoaki、Tashiro Mizuki、Yamamoto Yuki、Okada Morihito、Tahara Hidetoshi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 24 Pages: 7385-7385

    • DOI

      10.3390/jcm11247385

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunocyte Derived Exosomes: Insight into the Potential Chemo-immunotherapeutic Nanocarrier Targeting the Tumor Microenvironment2022

    • Author(s)
      Basak Moumita、Chaudhary Dharmendra Kumar、Takahashi Ryou-u、Yamamoto Yuki、Tiwari Swasti、Tahara Hidetoshi、Mittal Anupama
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 9 Issue: 1 Pages: 20-39

    • DOI

      10.1021/acsbiomaterials.2c00893

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PRPF19 regulates p53-dependent cellular senescence by modulating alternative splicing of MDM4 mRNA2021

    • Author(s)
      Yano Kimiyoshi、Takahashi Ryou-u、Shiotani Bunsyo、Abe Junko、Shidooka Tomoki、Sudo Yuki、Yamamoto Yusuke、Kan Shisei、Sakagami Hiroki、Tahara Hidetoshi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 297 Issue: 1 Pages: 100882-100882

    • DOI

      10.1016/j.jbc.2021.100882

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive serum and tissue microRNA profiling in dedifferentiated liposarcoma.2021

    • Author(s)
      Kohama Isaku、Asano Naofumi、Matsuzaki Juntaro、Yamamoto Yusuke、Yamamoto Tomofumi、Takahashi Ryou-U、Kobayashi Eisuke、Takizawa Satoko、Sakamoto Hiromi、Kato Ken、Fujimoto Hiroyuki、Chikuda Hirotaka、Kawai Akira、Ochiya Takahiro.
    • Journal Title

      Oncology Letters

      Volume: 22 Issue: 2 Pages: 623-623

    • DOI

      10.3892/ol.2021.12884

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規老化関連マイクロRNAはフェロトーシスを介して悪性胸膜中皮腫を抑制する2023

    • Author(s)
      山本 佑樹, 高橋 陵宇, 田原 栄俊
    • Organizer
      第82回日本癌学会総会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] miR-137-3pによる頭頸部扁平上皮がん抑制メカニズムの解明2023

    • Author(s)
      山本 佑樹、竹田 茉奈実、高橋 陵宇、田原 栄俊
    • Organizer
      第27回日本がん分子標的治療学会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵がん細胞における老化制御因子PRPF19の機能解析2023

    • Author(s)
      高橋 陵宇
    • Organizer
      第27回日本がん分子標的治療学会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RPF19 regulates p53-dependent cellular senescence by regulating alternative splicing of MDM4 mRNA2021

    • Author(s)
      高橋陵宇
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Book] 実験医学 2023年5月号 Vol.41 No.82023

    • Author(s)
      早野元詞,寺尾知可史
    • Total Pages
      133
    • Publisher
      羊土社
    • Related Report
      2023 Annual Research Report
  • [Book] 最新臨床大腸癌学20232023

    • Author(s)
      田中信治
    • Total Pages
      496
    • Publisher
      日本臨牀
    • Related Report
      2023 Annual Research Report
  • [Book] 腫瘍内科2023

    • Author(s)
      腫瘍内科編集委員会 編
    • Total Pages
      144
    • Publisher
      科学評論社
    • Related Report
      2023 Annual Research Report
  • [Remarks] 広島大学_研究者総覧

    • URL

      https://seeds.office.hiroshima-u.ac.jp/profile/ja.d1628e2cd12d1c64520e17560c007669.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] Research_map

    • URL

      https://researchmap.jp/rytakaha

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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