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Chromatin Remodeling Factors Correlate with Epithelial-Mesenchymal Transition of Lung adenocarcinoma

Research Project

Project/Area Number 23790413
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionThe University of Tokyo (2012)
Jichi Medical University (2011)

Principal Investigator

MATSUBARA Daisuke  東京大学, 医科学研究所, 講師 (80415554)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肺腺癌 / 肺癌 / クロマチンリモデリング / EMT / BRG1 / BRM / EMT / Lung adenocarcinoma
Research Abstract

BRG1 and BRM, two core catalytic subunits in SWI/SNF chromatin remodeling complexes, have been suggested as tumor suppressors, yet their roles in carcinogenesis are unclear. Here, we present evidence that loss of BRG1 and BRM is involved in the progression of lung adenocarcinomas. Analysis of 15 lung cancer cell lines indicated that BRG1 mutations correlated with loss of BRG1 expression and that loss of BRG1 and BRM expression was frequent in E-cadherin-low and vimentin-high cell lines. Immunohistochemical analysis of 93 primary lung adenocarcinomas showed loss of BRG1 and BRM in 11 (12%) and16 (17%) cases, respectively. Loss of expression of BRG1 and BRM was frequent in solid predominant adenocarcinomas and tumors with low thyroid transcription factor-1 (TTF-1,master regulator of lung) and low cytokeratin7 and E-cadherin (two markers for bronchial epithelial differentiation). Loss of BRG1 was correlated with the absence of lepidic growth patterns and was mutually exclusive of epidermal growth factor receptor (EGFR) mutations. In contrast, loss of BRM was found concomitant with lepidic growth patterns and EGFR mutations. Finally, we analyzed the publicly available dataset of 442 cases and found that loss of BRG1 and BRM was frequent in E-cadherin-low, TTF-1-low, and vimentin-high cases and correlated with poor prognosis. We conclude that loss of either or both BRG1 and BRM is involved in the progression of lung adenocarcinoma into solid predominant tumors with features of epithelial mesenchymal transition and loss of the bronchial epithelial phenotype. BRG1 loss wasspecifically involved in the progression of EGFR wild-type, but not EGFR-mutant tumors.

Report

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

    (21 results)

All 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (10 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Lung Cancerwith Loss of BRG1/BRM, shows Epithelial Mesenchymal Transition Phenotype and Distinct Histologic and Genetic Features.2013

    • Author(s)
      Matsubara D, Kishaba Y, Ishikawa S,Sakatani T, Oguni S, Tamura T,Hoshino H, Sugiyama Y, Endo S,Murakami Y, Aburatani H,Fukayama M, Niki T.
    • Journal Title

      Cancer Science

      Volume: 104(2) Pages: 266-73

    • Related Report
      2012 Final Research Report
  • [Journal Article] Lung cancer with loss of BRG1?BRM,shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features.2013

    • Author(s)
      Matsubara D, Murakami Y, Niki T et al.
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 2 Pages: 266-273

    • DOI

      10.1111/cas.12065

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of CCDC6-RET Fusion in a Human Lung Adenocarcinoma Cell Line, LC-2/ad.2012

    • Author(s)
      Matsubara D, Kanai Y, Ishikawa S,Ohara S, Yoshimoto T, Sakatani T, Oguni S,Tamura T, Kataoka H, Endo S, Murakami Y, Aburatani H, Fukayama M and Niki T.
    • Journal Title

      J Thorac Oncol.

      Volume: 7(12) Pages: 1872-6

    • Related Report
      2012 Final Research Report
  • [Journal Article] Epidermal Growth Factor Receptor Mutation and Chemosensitivity.2012

    • Author(s)
      Matsubara D, Niki T. (Letter to the Editor)
    • Journal Title

      J Thorac Oncol.

      Volume: 7(4) Pages: 771-772

    • Related Report
      2012 Final Research Report
  • [Journal Article] Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad.2012

    • Author(s)
      Matsubara D, Murakami Y, Niki T et al.
    • Journal Title

      J Thorac Oncol

      Volume: 7 Issue: 12 Pages: 1872-1876

    • DOI

      10.1097/jto.0b013e3182721ed1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] (Letter to the Editor) Epidermal Growth Factor Receptor Mutati on and Chemosensitivity2012

    • Author(s)
      Matsubara D, Niki T
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 7 Issue: 4 Pages: 771-772

    • DOI

      10.1097/jto.0b013e318245a058

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Pathologic & Genetic Feature of Lung Cancer with loss of BRG1/BRM:Correlation with EMT feature and lack of EGFR mutation2012

    • Author(s)
      Matsubara D, Kisyaba Y, Ishikawa S,Murakami Y, Aburatani H,Fukayama M, Niki T.
    • Organizer
      71th Annual Meeting of the Japanese Cancer Association(oral presentation)
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Final Research Report
  • [Presentation] Histopathologic and genetic featuresof lung adenocarcinomas with loss of chromatin remodeling factors, BRG-1 and BRM2012

    • Author(s)
      Matsubara D, Kishaba Y, Ishikawa S, Fukayama M, Niki T.
    • Organizer
      Annual Meeting of American Association for Cancer Research (poster presentation)
    • Place of Presentation
      Chicago
    • Related Report
      2012 Final Research Report
  • [Presentation] Pathologic & Genetic Feature of Lung Cancer with loss of BRG1/BRM:Correlation with EMT feature and lack of EGFR mutation2012

    • Author(s)
      Matsubara Daisuke
    • Organizer
      71th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] 原発性肺腺癌におけるクロマチンリモデリング因子BRG1及びBRMの欠損と上皮間葉系転換との関連性について2012

    • Author(s)
      松原 大祐
    • Organizer
      第53回日本肺癌学会総会
    • Place of Presentation
      岡山
    • Related Report
      2012 Annual Research Report
  • [Presentation] Histopathologic and genetic features of lung adenocarcinomas with loss of chromatin remodeling factors, BRG-1 and BRM.2012

    • Author(s)
      Matsubara Daisuke
    • Organizer
      Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Chicago, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Lung adenocarcinomas show genetic-morphologic correlations in three dimensional culture2011

    • Author(s)
      Matsubara D, Ishikawa S, Fukayama M, Niki T.
    • Organizer
      Annual Meeting of American Association for Cancer Research (poster presentation)
    • Place of Presentation
      Orlando
    • Related Report
      2012 Final Research Report
  • [Presentation] Lung adenocarcinomas show genetic-morphologic correlations in three dimensional culture.2011

    • Author(s)
      Matsubara D, Ishikawa S, Fukayama M, Niki T
    • Organizer
      Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Orlando
    • Related Report
      2011 Research-status Report
  • [Presentation] Expressions of bronchial epithelial markers correlate with morphology and genetic abnormalities in lung adenocarcinoma.2011

    • Author(s)
      Matsubara D, Ishikawa S, Fukayama M, Niki T.
    • Organizer
      70th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya
    • Related Report
      2011 Research-status Report
  • [Presentation] 肺腺癌症例の気管支上皮マーカーの発現に基づく分類:組織学的形態、遺伝子異常、EGFR,METの活性化との関連.2011

    • Author(s)
      松原大祐, 石川俊平,深山正久,仁木利郎.
    • Organizer
      第52回日本肺癌学会総会
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] 肺腺癌細胞株の遺伝子発現データに基づく分類と、3次元培養下の細胞形態、遺伝子異常との関連性について.2011

    • Author(s)
      松原大祐, 石川俊平,深山正久,仁木利郎.
    • Organizer
      第100回日本病理学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Book] <<標準臨床検査学>> 病理学・病理検査学 第二章 A 循環器系  B 呼吸器系  G 血液・造血器系 H 神経・感覚・運動器系2012

    • Author(s)
      松原 大祐
    • Total Pages
      296
    • Publisher
      医学書院
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/patholhttp://www.ims.u-tokyo.ac.jp/hitogan/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 最近の発表論文

    • URL

      http://www.jichi.ac.jp/pathol/index.php?%BA%C7%B6%E1%A4%CE%C8%AF%C9%BD%CF%C0%CA%B8

    • Related Report
      2012 Annual Research Report
  • [Remarks] 最近の学会発表

    • URL

      http://www.jichi.ac.jp/pathol/index.php?%BA%C7%B6%E1%A4%CE%B3%D8%B2%F1%C8%AF%C9%BD

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/pathol/

    • Related Report
      2011 Research-status Report

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

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