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上皮間葉系細胞転換(EMT)分子(NOTCH)を標的にした固形癌制御の研究

Research Project

Project/Area Number 19659211
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

長谷川 好規  Nagoya University, 大学院・医学系研究科, 教授 (20270986)

Co-Investigator(Kenkyū-buntansha) 橋本 直純  名古屋大学, 医学部附属病院, 助教 (30378020)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords上皮間葉系細胞転換 / Notch受容体 / 癌の転移 / 肺癌 / 血管内皮細胞 / アポトーシス / ルイス肺癌
Research Abstract

上皮細胞が間葉系細胞に変化する現象は、上皮間葉系細胞転換(EMT)として、またその逆の現象は間葉-上皮系細胞転換(MET)として知られており、この現象に関わる分子メカニズムについて精力的に研究が進められ、複数の分子が重要な役割を果たすことが報告されている。しかし、固形癌の進展・転移の成立におけるEMT/METの役割と分子メカニズムについてはまだ不明である。本研究では、EMT/METに関わる分子のなかでもTGF-βとともに重要な役割を果たすと考えられているNotch受容体とそのシグナル経路に焦点を絞り、その役割を明らかにする過程を通して、固形癌の進展・転移の成立におけるEMT/METの役割、さらには、Notch分子の発現や制御による固形癌制御の可能性を検討した。研究期間内に、(1)Notch細胞内ドメイン(NICD)の発現vectorの構築、(2)恒常的NICD発現細胞株の樹立、(3)apoptosis assay、(4)NICDサブクラスの影響の検討、(5)NICDの遺伝子導入におけるEMT機序への影響、について研究を実施した。その結果、肺癌細胞株においてNICDの発現誘導は、今回検討した細胞株においてアポトーシス誘導による抗腫瘍作用を示すことが示唆された。以前の報告からも、さまざまな組織由来の癌細胞においてNotchシグナルの作用には、腫瘍増殖作用を示す癌細胞株と腫瘍細胞死を示す癌細胞株が存在することが観察されていた。これらの報告とあわせて検討する場合、肺癌細胞においては、Notchシグナルは、増殖抑制および細胞死を誘導する可能性が示唆された。これらの所見は、肺癌の新たな治療戦略のtargetとなる可能性を示唆するのと同時にNotchシグナルの更なる解析の必要性を示唆していると考えられた。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (2 results) Book (1 results)

  • [Journal Article] A Novel Ca2+ influx pathway activated by mechanical strech in human airway smooth muscle cells.2008

    • Author(s)
      Ito S, et al.
    • Journal Title

      Am J Respir Cell Mol Biol 38

      Pages: 407-413

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual pathway activated by tert-butyl hydroperoxide in human airway anion secretion.2008

    • Author(s)
      Matsuno T, et al.
    • Journal Title

      J Pharmacol Exp Ther 327

      Pages: 453-464

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] YAPl is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation.2008

    • Author(s)
      Yokoyama T, et al.
    • Journal Title

      Carcmogenesis

      Pages: 2139-2146

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction.2008

    • Author(s)
      Ito S, et al.
    • Journal Title

      Pulm Pharmacol Ther 21

      Pages: 812-817

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of severity scoring systems A-DROP and CURB-65 for community-acquired pneumonia.2008

    • Author(s)
      Sindou Y, et al.
    • Journal Title

      Respirology 13

      Pages: 731-735

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Implication of clinical pathway care for community-acquired pneumonia in a community hospital : early switch from an intravenous beta-Iactam plus a macrolideto an oral respiratory fluoroquinolone.2008

    • Author(s)
      Sindou Y, et al.
    • Journal Title

      Intern Med 47

      Pages: 1865-1874

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SLCllAl (formerly NRAMP1) polymorphisms associated with multidrug-resistant tuberculosis.2008

    • Author(s)
      Takahasi K
    • Journal Title

      Tuberculosis 88

      Pages: 52-57

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TH1/TH2 immune response in lung fibroblasts in interstitial lung disease.2008

    • Author(s)
      Sumida A, et al.
    • Journal Title

      Arch Med Res 39

      Pages: 503-510

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemo-sensitivity to cisplatin, carboplatin and gemcitabine in human lung cancer cell lines.2008

    • Author(s)
      Shimizu J, et al.
    • Journal Title

      Respirology 13

      Pages: 510-517

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SLC11A1 (formerly NRAMP1) polymorphisms associated with multidrug-resistant tuberculosis.2008

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

      Tuberculosis 88

      Pages: 52-57

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage-derived chemokine in malignant and tuberculous pleural effusions.2007

    • Author(s)
      Okamoto M, et. al.
    • Journal Title

      Respirology 12

      Pages: 581-584

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] UGT1Al*6 and UGT1A1*27 for individualized irinotecan chemoth erapy.2007

    • Author(s)
      Ando Y, et. al.
    • Journal Title

      Curr Opin Mol Ther 9

      Pages: 258-262

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Induction of CXCR4 surface expression on microvascular endothelial cells by fourteen membered ring macrolldes.2008

    • Author(s)
      Hashimoto N, et al.
    • Organizer
      2008 International Conference of American Thoracic Society
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2008-05-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Different expression profile of Th1 and Th2 chemokines in UIP and NSIP.2008

    • Author(s)
      Honda T, et al.
    • Organizer
      2008 International Conference of American Thoracic Society
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2008-05-21
    • Related Report
      2008 Annual Research Report
  • [Book] 呼吸器疾患 最新の治療 2007-2009 XII.4.血液疾患(悪性リンパ腫、白血病)の肺病変2007

    • Author(s)
      長谷川好規
    • Total Pages
      506
    • Publisher
      南江堂(工藤翔二、中田紘一郎、貫和敏博 編集)
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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