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Loss of BTG2 expression in breast cancer progression

Research Project

Project/Area Number 23591906
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionJuntendo University

Principal Investigator

TAKAHASHI Fumiyuki  順天堂大学, 医学部, 准教授 (70327823)

Co-Investigator(Kenkyū-buntansha) NARA Takeshi  順天堂大学, 医学部, 准教授 (40276473)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords乳癌 / BTG2 / 転移 / 上皮間葉転換 / Lapatinib / EMT / 幹細胞 / microRNA
Research Abstract

EMT plays an important role in the tumor invasion and metastases. In human breast cancer, decreased BTG2 expression correlates with metastatic recurrence and decrease in overall survival, suggesting that suppression of BTG2 plays a critical role in disease progression. To analyze the role of BTG2 in breast cancer, BTG2 expression was knocked down in mammary epithelial cells. Suppression of BTG2 enhanced the motility of cells in vitro and enhanced tumor growth and metastasis in vivo. The effects of BTG2 knockdown were mediated through activation of HER2 and HER3, leading to elevated AKT phosphorylation. Suppression of HER activation using the lapatinib abrogated the effects of BTG2 knockdown, including the increased cell migration observed in vitro and the enhancement of tumorigenesis and metastasis in vivo. These results link BTG2-dependent effects on tumor progression, and raise the possibility that targeted inhibition of this pathway may be relevant in treatment breast cancers.

Report

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

    (28 results)

All 2014 2013 2012 2011 2010

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (9 results)

  • [Journal Article] Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor.2014

    • Author(s)
      Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, Nar a T, et al.
    • Journal Title

      PLoS One

      Volume: 28;9(1)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Genistein attenuates hypoxic pulmonary hypertension via NO and erythropoietin system2014

    • Author(s)
      Kuriyama S, Morio Y, Toba M, Nagaoka T, Takahashi F, Seyama K, Takahashi K.
    • Journal Title

      Am J Physiol - Lung Cell Mol Physiol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Genistein attenuates hypoxic pulmonary hypertension via NO and erythropoietin system2014

    • Author(s)
      Kuriyama S, Morio Y, Toba M, Nagaoka T, Takahashi F, et al.
    • Journal Title

      Am J Physiol - Lung Cell Mol Physiol

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tocilizumab, anti-interleukin 6 receptor antibody, the new approach to cancer cachexia2013

    • Author(s)
      Ando K, Takahashi F, Motojima S, Nakashima K, Kaneko N, Hoshi K, Takahashi K.
    • Journal Title

      J Clin Oncol

      Volume: 31(6)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Chronic intermittent hypoxia/reoxygenation facilitate amyloid-ß generation in mice2013

    • Author(s)
      Shiota S, Takekawa H, Matsumoto S, Takeda K, Nurwidya F, Yoshioka Y, Takahashi F, Hattori N, Tabira T, Motizuki H, Takahashi K.
    • Journal Title

      J Alzheimers Dis.

      Volume: 37(2) Pages: 325-33

    • Related Report
      2013 Final Research Report
  • [Journal Article] Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor2013

    • Author(s)
      Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, Nara T, Kato M, Tajima K, Shimada N, Iwakami S, Moriyama M, Moriyama H, Koizumi F, Takahashi K
    • Journal Title

      PLoS One

      Volume: 9(1) Issue: 1 Pages: e86459-e86459

    • DOI

      10.1371/journal.pone.0086459

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tocilizumab, anti-interleukin 6 receptor antibody, the new approach to cancer cachexia.2013

    • Author(s)
      Ando K, Takahashi F, et al.
    • Journal Title

      J Clin Oncol

      Volume: 31 Issue: 6 Pages: e69-e72

    • DOI

      10.1200/jco.2012.44.2020

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] HomeoboxB9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses2012

    • Author(s)
      Chiba N, Cornalis V, Shiotani B, Takahashi F, Shimada T., Tajima K., et al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109(8) Pages: 2760-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] Hypoxia induces gefitinib resistance in non-small cell lung cancer with both mutant and wild-type epidermal growth factor receptors.2012

    • Author(s)
      Minakata K, Takahashi F, Nar a T, Hashimoto M, Tajima K, Murakami A, Nurwidya F, et al.
    • Journal Title

      Cancer Science

      Volume: 103(11) Pages: 1946-54

    • Related Report
      2013 Final Research Report
  • [Journal Article] Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer2012

    • Author(s)
      Nurwidya F, Takahashi F, Murakami A, Takahashi K.
    • Journal Title

      Cancer Res Treat

      Volume: 44 Pages: 151-6

    • Related Report
      2013 Final Research Report
  • [Journal Article] a Kampo formula, ameliorates cancer cachexia induced by colon 26 adenocarcinoma in mice.2012

    • Author(s)
      Yae S, Takahashi F, Yae T, Yamaguchi T, Tsukada R, Koike K, Minakata K, Murakami A, Nurwidya F, Kato M, Tamada M, Yoshitake M, Kobayashi H, Seyama K, Takahashi K Hochuekkito (TJ-41)
    • Journal Title

      Evidence-Based Complementary and Alternative Medicine

      Volume: 2012 Pages: 976926-976926

    • Related Report
      2013 Final Research Report
  • [Journal Article] Lung cancer stem cells : Tumor biology and clinical implications2012

    • Author(s)
      Nurwidya F, Murakami A, Takahashi F, Takahashi K.
    • Journal Title

      Asia Pac J Clin Oncol

      Volume: 8 Pages: 217-222

    • Related Report
      2013 Final Research Report
  • [Journal Article] Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses.2012

    • Author(s)
      Chiba N, Cornalis V, Shiotani B, Takahashi F, et al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 8 Pages: 2760-5

    • DOI

      10.1073/pnas.1018867108

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors2012

    • Author(s)
      Minakata K, et al. (他12名)
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 11 Pages: 1946-1954

    • DOI

      10.1111/j.1349-7006.2012.02408.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Breast tumor progression induced by loss of BTG2 expression is inhibited by targeted therapy with the ErbB/HER2011

    • Author(s)
      Takahashi F, Chiba N, Tajima K, Hayashida T, Shimada T, Takahashi M, et al.
    • Journal Title

      inhibitor lapatinib Oncogene

      Volume: 30(27) Pages: 3084-95

    • Related Report
      2013 Final Research Report
  • [Journal Article] Breast tumor progression induced by loss of BTG2 expression is inhibited by targeted therapy with the ErbB/HER inhibitor lapatinib2011

    • Author(s)
      Takahashi F, Chiba N, Tajima K, et al.
    • Journal Title

      Oncogene

      Volume: 30 Pages: 3084-95

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 8. HoxB9, a gene overexpessed in breast cancer, promotes tumorigenicity and lung metastasis.2010

    • Author(s)
      Hayashida T, Takahashi F, Chiba N., Brachtel E., Takahashi M., et al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 107(3) Pages: 1100-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations2010

    • Author(s)
      Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, et al.
    • Journal Title

      Cell

      Volume: 141(1) Pages: 69-80

    • Related Report
      2013 Final Research Report
  • [Journal Article] Osteopontin mediates multidrug resistance of human mesothelioma cells through regulation of CD442010

    • Author(s)
      Tajima K, Ohashi R, Sekido Y, Hida T, Nar a T, Hashimoto M, Iwakami S, Minakata K, Yae T, Takahashi F, Saya H, and Takahashi K.
    • Journal Title

      binding to hyaluronate Oncogene

      Volume: 29(13) Pages: 1941-51

    • Related Report
      2013 Final Research Report
  • [Presentation] Tranilast inhibits pulmonary fibrosis by suppressing TGFβ-mediated extracellular matrix protein production.2013

    • Author(s)
      Kato M, Takahashi F, et al.
    • Organizer
      Asian Pacific Society of Respirology
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor.2013

    • Author(s)
      Murakami A, Takahashi F, et al.
    • Organizer
      Asian Pacific Society of Respirology
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Knockdown of zinc-finger E-box-binding homeobox 1 (ZEB1) reduces stem cells characteristic of gefitinib-resistant-persisters of PC9 cells.2013

    • Author(s)
      Nurwidya F, Takahashi F, et al.
    • Organizer
      Asian Pacific Society of Respirology
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of ZEB1 in hypoxia-induced epithelial mesenchymal transisition and stem cell features in NSCLC. (English poster session).2013

    • Author(s)
      Nurwidya F, Takahashi F, et al.
    • Organizer
      日本肺癌学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] BTG2発現低下による癌悪性化とEGFR-TKI治療感受性の検討2012

    • Author(s)
      高橋史行、高橋元美、田島健ら
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Related Report
      2013 Final Research Report
  • [Presentation] BTG2発現低下による癌悪性化とEGFR-TKI治療感受性の検討2012

    • Author(s)
      高橋史行、高橋元美、他
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report 2011 Research-status Report
  • [Presentation] 非小細胞肺癌の低酸素誘導性EGFR-TKI耐性機序におけるZEB1の関与2012

    • Author(s)
      村上朗子、高橋史行、他
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] BTG2発現低下による癌悪性化および上皮間葉転換(EMT)のメカニズムの検討2011

    • Author(s)
      高橋史行、高橋元美、田島健ら
    • Organizer
      日本呼吸器学会学術講演会
    • Related Report
      2013 Final Research Report
  • [Presentation] BTG2発現低下による癌悪性化および上皮間葉転換(EMT)のメカニズムの検討2011

    • Author(s)
      高橋史行、高橋元美ら
    • Organizer
      第51回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report

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

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