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Elucidation of the new mechanism for breast carcinogenesis associated with early endosome.

Research Project

Project/Area Number 25640061
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MIKI Yoshio  東京医科歯科大学, 難治疾患研究所, 教授 (10281594)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Akira  東京医科歯科大学, 難治疾患研究所, 准教授 (50321790)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords乳がん / BRCA2 / エンドサイトーシ / ESCRT複合体 / エンドサイトーシス / MT1-MMP
Outline of Final Research Achievements

We already reported that BRCA2 is involved in the abscission between two daughter cells during cytokinesis. The event of membrane abscission also occurs during endosome formation, so we made hypothesis that BRCA2 might have some role in the event of endosome formation through membrane abscission. We isolated endosome lysates from HeLa S3 cells and analyzed the lysates by mass spectrometry or immunoblotting using anti-BRCA2 antibody. The results indicated that the BRCA2 localizes at early endosome. Furthermore, BRCA2 and GFP-Rab5, which was over expressed as a marker of early endosome, were showed the co-localization using immunofluorescence microscopy. However, the interaction of both proteins are still unclear from the immunoblotting data using total whole cell lysates. Then, we tried the mass spectrometry analysis of the anti-BRCA2 immunoprecipitates from endosome lysates. This results suggested the possibility of new BRCA2 function at early endosome.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients.2014

    • Author(s)
      Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, Thiery JP.
    • Journal Title

      EMBO Mol Med.

      Volume: 6 Issue: 12 Pages: 1279-1293

    • DOI

      10.4161/cc.28896

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BRCA2 phosphorylated by PLK1 moves to the midbody to regulate cytokinesis mediated by nonmuscle myosin IIC.2014

    • Author(s)
      Takaoka, Saito, Takenaka, Miki, and Nakanishi
    • Journal Title

      Cancer Research

      Volume: 74 Issue: 5 Pages: 1518-1528

    • DOI

      10.1158/0008-5472.can-13-0504

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Centrosomal BRCA2 is a target protein of membrane type-1 matrix metalloproteinase (MT1-MMP).2014

    • Author(s)
      Wali N, Hosokawa K, Malik S, Saito H, Miyaguchi K, Imajoh-Ohmi S, Miki Y, Nakanishi A.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 443 Issue: 4 Pages: 1148-1154

    • DOI

      10.1016/j.bbrc.2013.12.103

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] M期中心体におけるMT1-MMPのBRCA2タンパク分解2014

    • Author(s)
      10.高岡 美帆、ナディラ ワリ、斎藤 広子、中西 啓、三木 義男
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規BRCA機能とそれに基づく合成致死療法の開発2013

    • Author(s)
      三木義男
    • Organizer
      第51回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Functional analysis of a cleavage product of BRCA2 in cancer cell lines2013

    • Author(s)
      Nadila Wali, Kana Hosokawa, Hiroko Saito, Shinobu Ohmi, Akira Nakanishi, Yoshio Miki,
    • Organizer
      ASCB 2013 Annual meeting,
    • Place of Presentation
      New Orleans, LA, USA,
    • Related Report
      2013 Research-status Report
  • [Presentation] 遺伝性乳癌患者でみられるBRCA2 遺伝子内の変異が細胞質分裂に与える影響.2013

    • Author(s)
      高岡美帆、斉藤広子、中西啓、三木義男
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Remarks] 東京医科歯科大学 難治疾患研究所 分子遺伝分野

    • URL

      http://www.tmd.ac.jp/mri/mgen/index_j.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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