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Unravelling the mechanism of ovarian carcinogenesis caused by BRCA1 depletion and estrogen action

Research Project

Project/Area Number 26670730
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

OHTA Tomohiko  聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (60233136)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsBRCA1 / エストロゲン / 卵管癌 / DNA損傷 / ヘテロクロマチン
Outline of Final Research Achievements

The mechanism of tissue specificity; how BRCA1 mutation specifically triggers only breast and ovarian cancer, has been unrevealed. In this study we established doxycyclin-inducible BRCA1 deficient and estrogen receptor α (ERα) positive diploid human breast cell lines and investigated the effect of estrogen receptor expression on genomic and epigenomic stability in BRCA1-defective cellular background. BRCA1-depleted/ERα-positive cells exhibited chromatin de-compaction, increase of G2/M phase population and apoptosis, accompanied by significant cell number reduction, in response to doxycyclin treatment when compared to control BRCA1-depleted or ERα-positive cells.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2016 2015 2014 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (9 results) Remarks (2 results)

  • [Journal Article] Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response.2016

    • Author(s)
      Fukuda T, Tsuruga T, Kuroda T, Nishikawa H, Ohta T.
    • Journal Title

      Curr Cancer Drug Targets.

      Volume: 16(2) Issue: 2 Pages: 101-9

    • DOI

      10.2174/1568009615666151030102427

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌の発症と治療におけるユビキチン系の役割2016

    • Author(s)
      扇屋りん, 太田智彦
    • Journal Title

      医学のあゆみ

      Volume: 256 Pages: 868-873

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Interaction of BARD1 and HP1 Is Required for BRCA1 Retention at Sites of DNA Damage.2015

    • Author(s)
      Wu W, Nishikawa H, Fukuda T, Vittal V, Asano M, Miyoshi Y, Klevit RE, Ohta T
    • Journal Title

      Cancer Res

      Volume: 75 Issue: 7 Pages: 1311-1321

    • DOI

      10.1158/0008-5472.can-14-2796

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The BARD1/HP1 interaction: another clue about heterochromatin involvement in homologous recombination2015

    • Author(s)
      Fukuda T, Tsuruga T, Kuroda T, Takeuchi J, Wu W, Ohta T
    • Journal Title

      Molecular & Cellular Oncology

      Volume: aEpub ahead of print Issue: 2 Pages: 1-3

    • DOI

      10.1080/23723556.2015.1030535

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] MED12 exon 2 mutations in phyllodes tumors of the breast2015

    • Author(s)
      Nagasawa S, Maeda I, Fukuda T, Wu W, Hayami R, Kojima Y, Tsugawa KI, Ohta T
    • Journal Title

      Cancer Med

      Volume: Epub ahead of print Issue: 7 Pages: 1-5

    • DOI

      10.1002/cam4.462

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Class I HDAC inhibitors inhibit the retention of BRCA1 and 53BP1 at the site of DNA damage2015

    • Author(s)
      Fukuda T,Wu W, Okada M,Maeda I, Kojima Y, Hayami R, Miyoshi Y, Tsugawa K, Ohta T
    • Journal Title

      Cancer Science

      Volume: 106 Issue: 8 Pages: 1050-1056

    • DOI

      10.1111/cas.12717

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Liganded ERα stimulates the E3 ubiquitin ligase activity of UBE3C to facilitate cell proliferation2015

    • Author(s)
      Okada M, Ohtake F, Nishikawa H, Wu W, Saeki Y, Takana K, Ohta T
    • Journal Title

      Molecular Endocrinology

      Volume: 29 Issue: 11 Pages: 1646-1657

    • DOI

      10.1210/me.2015-1125

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NF-kB signaling mediates acquired resistance after PARP inhibition.2015

    • Author(s)
      Nakagawa Y, Sedukhina AS, Okamoto N, Nagasawa S, Suzuki N, Ohta T, Hattori H, Roche-Molina M, Narváez AJ, Jeyasekharan AD, Bernal JA, Sato K.
    • Journal Title

      Oncotarget.

      Volume: 6 Pages: 3825-3839

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interaction of BARD1 and HP1 is required for BRCA1 retention at sites of DNA damage.2015

    • Author(s)
      Wu W, Nishikawa H, Fukuda T, Vittal V, Asano M, Miyoshi Y, Klevit RE, Ohta T.
    • Journal Title

      Cancer Res.

      Volume: 75 Pages: 1311-1321

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer, and Sensitivity to PARP Inhibition.2015

    • Author(s)
      Nagasawa S, Sedukhina AS, Nakagawa Y, Maeda I, Kubota M, Ohnuma S, Tsugawa K, Ohta T, Roche-Molina M, Bernal JA, Narváez AJ, Jeyasekharan AD, Sato K.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 2 Pages: e0118002-e0118002

    • DOI

      10.1371/journal.pone.0118002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin acetylation inhibits polyubiquitin chain elongation.2015

    • Author(s)
      Ohtake F, Saeki Y, Sakamoto K, Ohtake K, Nishikawa H, Tsuchiya H, Ohta T, Tanaka K, Kanno J.
    • Journal Title

      EMBO Rep.

      Volume: 16 Issue: 2 Pages: 192-201

    • DOI

      10.15252/embr.201439152

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HERC2 and its interactors in regulation of DNA damage response and cell cycle.2015

    • Author(s)
      太田智彦
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] トランスレーショナルリサーチを進める上での問題点2015

    • Author(s)
      太田智彦, 前田一郎, 津川浩一郎
    • Organizer
      第23回日本乳癌学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] BRCA1 retention at DNA double-strand breaks in homology-directed repair pathways2014

    • Author(s)
      Tomohiko Ohta
    • Organizer
      International Symposium on Homeostasis through development, life, and diseases
    • Place of Presentation
      群馬大学(群馬県前橋市)
    • Year and Date
      2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] HP1 amma mediates BARD1 retention on Lys9-dimethylated histone H3 at sites of DNA damage2014

    • Author(s)
      Tomohiko Ohta, Hiroyuki Nishikawa, Anna S. Sedukhina, Takayo Fukuda, Wenwen Wu
    • Organizer
      Fusion Conference DNA Replication as a Source of DNA Damage
    • Place of Presentation
      カサブランカ(モロッコ)
    • Year and Date
      2014-10-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Therapeutic strategy targeting the mechanism of BRCA1 retention at DNA damage sites via a histone modification.2014

    • Author(s)
      太田智彦
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] ATM-dependent but RNF168-independent BRCA1/BARD1 retention at sites of DNA damage2014

    • Author(s)
      Tomohiko Ohta, Hiroyuki Nishikawa, Anna S. Sedukhina, Takayo Fukuda, Wenwen Wu
    • Organizer
      Benzon Symposium No 60 - Nuclear Regulation by Ubiquitin
    • Place of Presentation
      コペンハーゲン(デンマーク)
    • Year and Date
      2014-08-18
    • Related Report
      2014 Research-status Report
  • [Presentation] BRCA1のDNA損傷応答とヒストン修飾2014

    • Author(s)
      太田智彦
    • Organizer
      第19回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府豊中市)
    • Year and Date
      2014-08-09
    • Related Report
      2014 Research-status Report
  • [Presentation] BRCA1の新規DNA損傷応答メカニズムを標的とした治療戦略2014

    • Author(s)
      太田智彦
    • Organizer
      第22回日本乳癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-07-10
    • Related Report
      2014 Research-status Report
  • [Presentation] BRCA1の新規クロマチン結合機構を標的としたがん治療戦略2014

    • Author(s)
      太田智彦
    • Organizer
      第15回ホルモンと癌研究会
    • Place of Presentation
      艮陵会館(宮城県仙台市)
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report
  • [Remarks] 聖マリアンナ医科大学大学院 医学研究科 応用分子腫瘍学

    • URL

      http://www.marianna-u.ac.jp/t-oncology/results/all.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 聖マリアンナ医科大学大学院 医学研究科 応用分子腫瘍学

    • URL

      http://www.marianna-u.ac.jp/t-oncology/index.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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