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Elucidation of estrogen receptor-mediated transcription regulatory systems and downstream signaling pathways in breast cancer and clinical application to cancer management

Research Project

Project/Area Number 26293223
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Endocrinology
Research InstitutionSaitama Medical University

Principal Investigator

HORIE KUNIKO  埼玉医科大学, 医学部, 教授 (90261982)

Co-Investigator(Renkei-kenkyūsha) INOUE SATOSHI  埼玉医科大学, 医学部, 客員教授 (40251251)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords乳がん / エストロゲン受容体 / ホルモン治療抵抗性 / 長鎖非コードRNA / マイクロRNA / RNAシーケンス / バイオマーカー / 内科
Outline of Final Research Achievements

Based on high-throughput sequencing using estrogen-sensitive and hormone therapy-refractory model breast cancer cells, we identified several long noncoding RNAs that are transcribed from the vicinity of estrogen receptor binding sites and exhibit estrogen-dependent expression. We found that the siRNA-mediated knockdown of these noncoding RNAs inhibited the growth of breast cancer cells including hormone therapy-refractory types and the growth of breast cancer cell-derived tumors inoculated in nude mice. Based on functional screenings, we identified several relevant factors and microRNAs together with their target genes, which have associations with prognosis of breast cancer patients. Those molecules could be clinically applied to diagnostic and therapeutic targets for breast cancer management.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (15 results)

All 2016 2015 2014 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Estrogen modulates exercise endurance along with mitochondrial uncoupling protein 3 downregulation in skeletal muscle of female mice.2016

    • Author(s)
      Nagai S, Ikeda K, Horie-Inoue K, Shiba S, Nagasawa S, Takeda S, Inoue S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 480 Issue: 4 Pages: 758-784

    • DOI

      10.1016/j.bbrc.2016.10.129

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ABHD2, an androgen target gene, promotes prostate cancer cell proliferation and migration.2016

    • Author(s)
      Obinata D, Takada S, Takayama K, Urano T, Ito A, Ashikari D, Fujiwara K, Yamada Y, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y
    • Journal Title

      Eur J Cancer 57

      Volume: 57 Pages: 39-49

    • DOI

      10.1016/j.ejca.2016.01.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A2015

    • Author(s)
      Ikeda K, Horie-Inoue K, Ueno T, Suzuki T, Sato W, Shigekawa T, Osaki A, Saeki T, Berezikov E, Mano H, Inoue S
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 13170-13170

    • DOI

      10.1038/srep13170

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] MicroRNA-574-3p, identified by microRNA library-based functional screening, modulates tamoxifen response in breast cancer2015

    • Author(s)
      Ujihira T, Ikeda K, Suzuki T, Yamaga R, Sato W, Horie-Inoue K, Shigekawa T, Osaki A, Saeki T, Okamoto K, Takeda S, Inoue S
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 7641-7641

    • DOI

      10.1038/srep07641

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes2014

    • Author(s)
      Miyazaki T, Ikeda K, Horie-Inoue K, Kondo T, Takahashi S, Inoue S
    • Journal Title

      Oncogenesis

      Volume: 3 Issue: 11 Pages: e126-e126

    • DOI

      10.1038/oncsis.2014.40

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Functional shRNA library screening and sequencing-based identification of coding and non-coding RNAs that associate with the biology of hormone refractory cancers.2016

    • Author(s)
      Kuniko Horie
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ホルモン依存性がんにおける長鎖非コードRNAの役割.2015

    • Author(s)
      堀江公仁子、池田和博、井上聡
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] A stabilizing factor for mitochondrial respiratory supercomplex assembly facilitates breast tumor growth in hypoxia.2015

    • Author(s)
      Ikeda K, Horie-Inoue K, Inoue S
    • Organizer
      EMBO Meeting, Nuclear receptors: From molecules to humans.
    • Place of Presentation
      アジャクシオ(コルシカ島、フランス)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integrated analysis identified estrogen-dependent FOXP1 actions on G protein-coupled receptor signaling in breast cancer cells.2015

    • Author(s)
      Horie-Inoue K, Ikeda K, Inoue S
    • Organizer
      FASEB Science Research Conferences. Molecular and Systems Integration of Genomic and Nongenomic Steroid Hormone Action.
    • Place of Presentation
      ビッグスカイ(モンタナ州、米国)
    • Year and Date
      2015-08-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ホルモン応答性長鎖非コードRNAの同定・機能の解明と抗加齢医学への応用.2015

    • Author(s)
      堀江公仁子、井上聡
    • Organizer
      第15回日本抗加齢医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2015-05-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Gene regulatory networks mediated by estrogen receptor and forkhead transcription factors in breast cancer2015

    • Author(s)
      Horie-Inoue K, Ikeda K, Inoue S
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Systems Biology: Networks
    • Place of Presentation
      Cold Spring Habor Laboratory, NY, USA
    • Year and Date
      2015-03-17 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 乳がんの病態進行にかかわるアンチセンス長鎖非コードRNA の同定と機能解析2014

    • Author(s)
      堀江公仁子、池田和博、井上聡
    • Organizer
      第22回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      都道府県会館(東京都千代田区)
    • Year and Date
      2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Remarks] 埼玉医科大学ゲノム医学研究センター遺伝子情報制御部門

    • URL

      http://www.saitama-med.ac.jp/genome/Div02_GRST/index.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 二本鎖核酸分子、DNA、ベクター、癌細胞増殖抑制剤、癌細胞移動抑制剤、及び医薬2015

    • Inventor(s)
      井上聡、池田和博、堀江公仁子
    • Industrial Property Rights Holder
      井上聡、池田和博、堀江公仁子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-06-12
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 二本鎖核酸分子、DNA,ベクター、癌細胞増殖抑制剤、及び医薬2014

    • Inventor(s)
      井上聡、池田和博、堀江公仁子
    • Industrial Property Rights Holder
      井上聡、池田和博、堀江公仁子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-122067
    • Filing Date
      2014-06-13
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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