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Proliferation of breast cancer stem cells via NO/cGMP signaling pathway

Research Project

Project/Area Number 23590322
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionNational Institute of Health Sciences

Principal Investigator

KANDA Yasunari  国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)

Co-Investigator(Kenkyū-buntansha) ISHIDA Seiichi  国立医薬品食品衛生研究所, 薬理部第三室, 室長 (10270505)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords癌幹細胞 / エストロゲン / NO / cGMP / PKG / 増殖 / 乳癌 / 活性酸素
Research Abstract

Growing evidence suggests that development of breast cancer is originated from cancer stem cells, which can be isolated by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, the growth regulation of cancer stem cells has not been fully understood. In the present study, we found that estrogen increased the size of ALDH-positive cell population in MCF-7 cells. The effect of estrogen was inhibited by the estrogen receptor (ER) antagonist ICI182780. We next examined the downstream pathway from the ER. A selective NOS inhibitor inhibited the effect of estrogen on NO production and the size of ALDH-positive cell population. In addition, 8-Br-cGMP mimicked the effect of estrogen. Taken together, these data suggest the estrogen expands breast cancer stem cells through the NO/cGMP signaling pathway.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (64 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 7 results) Presentation (48 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Assessment of Testing Methods for Drug-Induced Repolarization Delay and Arrhythmias in an iPS Cell–Derived Cardiomyocyte Sheet: Multi-site Validation Study2014

    • Author(s)
      Nakamura Y., Matsuo J., Miyamoto N., Ojima A., Ando K., Kanda Y., Sawada K., Sugiyama A., Sekino Y.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Issue: 4 Pages: 494-501

    • DOI

      10.1254/jphs.13248FP

    • NAID

      130003391508

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells2013

    • Author(s)
      Yamada S., Kotake Y., Sekino Y. and Kanda Y.
    • Journal Title

      Metallomics

      Volume: 5 Pages: 484-491

    • Related Report
      2013 Final Research Report
  • [Journal Article] Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death2013

    • Author(s)
      Ishida K., Kotake Y., Miyara M., Aoki K., Sanoh S., Kanda Y., Ohta S.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 3 Pages: 513-521

    • DOI

      10.2131/jts.38.513

    • NAID

      10031158917

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Developing and standardizing experimental protocols using human iPS-derived cells to predict adverse drug reactions in pre-clinical safety studies2013

    • Author(s)
      Sekino Y, Sato K, Kanda Y, Ishida S.
    • Journal Title

      Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku

      Volume: 131 Pages: 25-34

    • NAID

      40019879865

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells2013

    • Author(s)
      Yamada S, Kotake Y, Sekino Y, Kanda Y
    • Journal Title

      Metallomics

      Volume: 5(5) Issue: 5 Pages: 484-91

    • DOI

      10.1039/c3mt20268b

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ヒトiPS細胞から心筋細胞への分化誘導法2013

    • Author(s)
      諫田泰成
    • Journal Title

      日本薬理学会誌

      Volume: 141 Pages: 32-36

    • Related Report
      2012 Research-status Report
  • [Journal Article] Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human induced pluripotent stem cells2012

    • Author(s)
      Kuroda T., Yasuda S., Kusakawa S., Hirata N., Kanda Y., Suzuki K., Takahashi M., Nishikawa S., Kawamata S, Sato Y.
    • Journal Title

      PLoS ONE

      Volume: 7

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role ofα7-nicotinic acetylcholine receptor in normal and cancer stem cells2012

    • Author(s)
      Lin W., Hirata N., Sekino Y., Kanda Y
    • Journal Title

      Current Drug Targets

      Volume: 13 Pages: 656-665

    • Related Report
      2013 Final Research Report
  • [Journal Article] Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human induced pluripotent stem cells2012

    • Author(s)
      Kuroda T., Yasuda S., Kusakawa S., Hirata N., Kanda Y., Suzuki K., Takahashi M., Nishikawa S., Kawamata S and Sato Y.
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 5 Pages: e37342-e37342

    • DOI

      10.1371/journal.pone.0037342

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of α7-nicotinic acetylcholine receptor in normal and cancer stem cells.2012

    • Author(s)
      Lin W., Hirata N., Sekino Y. and Kanda Y.
    • Journal Title

      Current Drug Targets

      Volume: 13 Issue: 5 Pages: 656-665

    • DOI

      10.2174/1389450111209050656

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ヒト幹細胞を用いた医薬品の安全性評価2012

    • Author(s)
      諫田泰成
    • Journal Title

      ファルマシア

      Volume: 48 Pages: 862-867

    • NAID

      110009901188

    • Related Report
      2012 Research-status Report
  • [Journal Article] Reactive oxygen species mediate adipocyte differentiation in mesenchymal stem cells.2011

    • Author(s)
      Kanda Y, Hinata T, Kang SW, Watanabe Y.
    • Journal Title

      Life Sciences

      Volume: 89 Pages: 250-258

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] S1PR3は乳癌幹細胞に対する新規標的分子である2014

    • Author(s)
      平田尚也, 山田茂, 正田卓司, 栗原正明, 関野祐子, 諫田泰成
    • Organizer
      第87回日本薬理学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞の増殖に対するスフィンゴシン1リン酸受容体S1PR3の影響2014

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都
    • Year and Date
      2014-03-06
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel role of sphingosine-1-phosphate receptor S1PR3 in cancer stem cell expansion via a Notch-dependent pathway2014

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Shigeru Yamada, Yuko Sekino
    • Organizer
      Keystone symposium
    • Place of Presentation
      Canada
    • Year and Date
      2014-02-04
    • Related Report
      2013 Final Research Report
  • [Presentation] スフィンゴシン1リン酸受容体S1PR3を介した乳癌幹細胞の増殖機構2013

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第129回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2013-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitroおよびin vivoにおけるmammosphereの増殖に対するニコチンの影響2013

    • Author(s)
      平田尚也, 諫田泰成
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌幹細胞を標的とした創薬の可能性2013

    • Author(s)
      諫田泰成
    • Organizer
      第36回日本生物工学会
    • Place of Presentation
      広島
    • Year and Date
      2013-09-20
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] NO/sGC/cGMP経路を介した乳癌幹細胞の増殖2013

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of sphingosine kinase in cancer stem cells2013

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Shigeru Yamada, Yuko Sekino
    • Organizer
      FASEB Summer Research Conference
    • Place of Presentation
      Niseko, Japan
    • Year and Date
      2013-08-07
    • Related Report
      2013 Final Research Report
  • [Presentation] ADAM17 mediates cancer stem cell phenotype in MCF-7 cells2013

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2013-05-17
    • Related Report
      2013 Final Research Report
  • [Presentation] TGFβ刺激によるNotchシグナルを介した乳癌幹細胞の増殖機構2013

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞におけるニコチンとNotchシグナルのクロストーク2013

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌幹細胞の受容体を標的とした治療戦略2013

    • Author(s)
      諫田泰成
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-21
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 乳癌幹細胞におけるスフィンゴシン1リン酸とNotchシグナルのクロストーク2012

    • Author(s)
      諫田泰成, 平田尚也, 山田茂, 関野祐子
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌幹細胞を標的とする薬剤の可能性2012

    • Author(s)
      諫田泰成
    • Organizer
      第127回薬理学会関東部会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] TGFβ刺激によるMEK/ERKを介した乳癌幹細胞の増殖2012

    • Author(s)
      平田尚也, 諫田泰成
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞の増殖に対するTGFβの影響2012

    • Author(s)
      平田尚也, 山田茂, 関野祐子, 諫田泰成
    • Organizer
      日本薬理学会第126回関東部会
    • Place of Presentation
      東京
    • Year and Date
      2012-07-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞におけるリゾリン脂質の機能解析2012

    • Author(s)
      諫田泰成
    • Organizer
      第11回生命科学研究会
    • Place of Presentation
      秋田
    • Year and Date
      2012-06-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Role ofα7 nicotinic acetylcholine receptor in cancer stem cells2012

    • Author(s)
      Naoya Hirata, Yuko Sekino, Yasunari Kanda
    • Organizer
      10^<th> International Society for Stem Cell Research
    • Place of Presentation
      Yokohama
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of breast cancer stem cells by sphingosine-1-phosphate2012

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino
    • Organizer
      10^<th> International Society for Stem Cell Research
    • Place of Presentation
      Yokohama
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of sphingosine kinase-1 in proliferation of cancer stem cells2012

    • Author(s)
      諫田泰成
    • Organizer
      第10回幹細胞シンポジウム
    • Place of Presentation
      淡路島
    • Year and Date
      2012-05-31
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] エストロゲン刺激による乳癌幹細胞の増殖に対するSrcの影響2012

    • Author(s)
      平田尚也, 関野祐子, 諫田泰成
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-14
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] 乳癌幹細胞におけるスフィンゴシン1リン酸とNotchシグナルのクロストーク2012

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino
    • Organizer
      Keystone Symposia (Q3)
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2012-02-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Sphingolipid-mediated proliferation of cancer stem cells.2012

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino.
    • Organizer
      Keystone Symposia
    • Place of Presentation
      バンフ(カナダ)
    • Related Report
      2011 Research-status Report
  • [Presentation] トリブチルスズのミトコンドリア機能に対する影響2012

    • Author(s)
      諫田泰成、平田尚也、山田茂、関野祐子
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] 癌幹細胞を標的とする薬剤の可能性2011

    • Author(s)
      諫田泰成, 平田尚也, 関野祐子
    • Organizer
      第34回分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] TGFβ刺激によるMEK/ERKを介した乳癌幹細胞の増殖2011

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino
    • Organizer
      FASEB summer conference
    • Year and Date
      2011-08-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞の増殖に対するTGFβの影響2011

    • Author(s)
      平田尚也, 林和花, 関野祐子, 諫田泰成
    • Organizer
      第124回薬理学会関東部会
    • Year and Date
      2011-06-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌幹細胞におけるリゾリン脂質の機能解析2011

    • Author(s)
      諫田泰成, 平田尚也, 林和花, 関野祐子
    • Organizer
      第9回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-05-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Effects of sex hormones on proliferation of breast cancer stem cell.2011

    • Author(s)
      諫田泰成、平田尚也、林和花、関野祐子
    • Organizer
      第9回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] エストロゲン刺激による乳癌幹細胞の増殖2011

    • Author(s)
      平田尚也、林和花、関野祐子、諫田泰成
    • Organizer
      第124回薬理学会関東部会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Sphingosine-1-phosphate mediates proliferation of breast cancer stem cells.2011

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino
    • Organizer
      FASEB summer conference
    • Place of Presentation
      ルッカ(イタリア)
    • Related Report
      2011 Research-status Report
  • [Presentation] 乳癌幹細胞の増殖に対するスフィンゴシン1リン酸の作用2011

    • Author(s)
      諫田泰成、平田尚也、関野祐子
    • Organizer
      第34回分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] ADAM17 mediates cancer stem cell phenotype in MCF-7 cells

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of sphingosine kinase in cancer stem cells

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Shigeru Yamada, Yuko Sekino
    • Organizer
      FASEB Summer Research Conference
    • Place of Presentation
      ニセコ
    • Related Report
      2013 Annual Research Report
  • [Presentation] NO/sGC/cGMP経路を介した乳癌幹細胞の増殖

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitroおよびin vivoにおけるmammosphereの増殖に対するニコチンの影響

    • Author(s)
      平田尚也、諫田泰成
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] A novel role of sphingosine-1-phosphate receptor S1PR3 in cancer stem cell expansion via a Notch-dependent pathway

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Shigeru Yamada, and Yuko Sekino
    • Organizer
      Keystone symposia
    • Place of Presentation
      カナダ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 乳癌幹細胞の増殖に対するスフィンゴシン1リン酸受容体S1PR3の影響

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] S1PR3は乳癌幹細胞に対する新規標的分子である

    • Author(s)
      平田尚也、山田茂、正田卓司、栗原正明、関野祐子、諫田泰成
    • Organizer
      第87回日本薬理学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 乳癌幹細胞におけるリゾリン脂質の機能解析

    • Author(s)
      諫田泰成、平田尚也、山田茂、関野祐子
    • Organizer
      第11回生命科学研究会
    • Place of Presentation
      秋田
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of α7 nicotinic acetylcholine receptor in cancer stem cells

    • Author(s)
      Naoya Hirata, Yuko Sekino, Yasunari Kanda
    • Organizer
      10th International Society for Stem Cell Research
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of breast cancer stem cells by sphingosine-1-phosphate

    • Author(s)
      Yasunari Kanda, Naoya Hirata, Yuko Sekino
    • Organizer
      10th International Society for Stem Cell Research
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 乳癌幹細胞の増殖に対するTGFβの影響

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      日本薬理学会第126回関東部会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] TGFβ刺激によるMEK/ERKを介した乳癌幹細胞の増殖

    • Author(s)
      平田尚也、諫田泰成
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 癌幹細胞を標的とする薬剤の可能性

    • Author(s)
      諫田泰成
    • Organizer
      第127回薬理学会関東部会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 乳癌幹細胞におけるスフィンゴシン1リン酸とNotchシグナルのクロストーク

    • Author(s)
      諫田泰成、平田尚也、山田茂、関野祐子
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] TGFβ刺激によるNotchシグナルを介した乳癌幹細胞の増殖機構

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 乳癌幹細胞におけるニコチンとNotchシグナルのクロストーク

    • Author(s)
      平田尚也、山田茂、関野祐子、諫田泰成
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Book] Cancer Stem Cells - Fact or Fiction? (Chapter1). Role of Cancer Stem Cells in Cancer Biology and Therapy2013

    • Author(s)
      Kanda Y
    • Publisher
      CRC Press
    • Related Report
      2013 Final Research Report
  • [Book] Role of Cancer Stem Cells in Cancer Biology and Therapy.2013

    • Author(s)
      Y Kanda
    • Total Pages
      22
    • Publisher
      CRC press
    • Related Report
      2013 Annual Research Report
  • [Book] Isolation and characterization of cancer stem cells using flow cytometry (Chapter6, p107-124). Clinical Flow Cytometry–Emerging Applications2012

    • Author(s)
      Kanda Y
    • Publisher
      InTech
    • Related Report
      2013 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.nihs.go.jp/phar/lab/lab2.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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