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TNF induced lung injury was protected by EGFR transactivation

Research Project

Project/Area Number 21790788
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

YAMAOKA Toshimitsu  昭和大学, 腫瘍分子生物学研究所, 講師 (40384359)

Project Period (FY) 2009 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肺癌 / 肺障害 / 上皮成長因子受容体 / 腫瘍壊死因子 / 急性肺障害 / EGFR / TNF-alpha / apoptosis / TACE / アポトーシス / 肺線維症
Research Abstract

EGFR tyrosine kinase activity protects TNF-induced lung epithelial cells apoptosis and this might be the mechanism of EGFR tyrosine kinase inhibitor (TKI)-induced lung injury. In this study, to the purpose of clarifying the mechanisms, we employed the SPC/TNF-transgenic mice, which over-expressed TNF in alveolar type 2 cells under the control of the human surfactant protein C promoter, resulted in interstitial pneumonia and pulmonary fibrosis chronically. EGFR-TKI, Gefitinib was orally administrated for this mice, then we observed worsened the lung injury. This novel observation has significant implications for understanding the role of EGFR in maintaining human lung epithelial cell homeostasis in an environment of inflammation, injury/repair, such as inflammation-associated carcinogenesis and cancer promotion.

Report

(5 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (16 results)

All 2012 2011 2010 2009 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (11 results) Book (1 results) Remarks (1 results)

  • [Journal Article] EGFR阻害剤の耐性とその克服 (The mechanisms of resistance to EGFR-TKIs and challenges to overcome resistance in EGFR mutant Non-small cell lung cancer)2012

    • Author(s)
      山岡利光, 大森亨
    • Journal Title

      癌と化学療法

      Volume: 39巻6号 Pages: 857-862

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific epidermal growth factor receptor autophosphorylation sites promote mouse colon epithelial cell chemotaxis and restitution2011

    • Author(s)
      Yamaoka T, Frey MR, Dise RS, Bernard JK, Polk DB
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 301(2)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific epidermal growth factor receptor autophosphorylation sites promote mouse colon epithelial cell chemotaxis and restitution2011

    • Author(s)
      山岡利光
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 301 Pages: 368-376

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Specific epidermal growth factor receptor autophosphorylation sites promote epithelial cell chemotaxis and restitution2012

    • Author(s)
      Toshimitsu Yamaoka, Mark Frey, D. Brent Polk, Yasunari Oki, Yasunori Murata, Tomohide Sugiyama, Sojiro Kusumoto, Hiroo Ishida, Takao Shirai, Masanao Nakashima, Kentaro Okuda, Tsukasa Ohnishi, Takashi Hirose, Tohru Ohmori and Mitsuru Adachi
    • Organizer
      103rd Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Chicago
    • Related Report
      2012 Final Research Report
  • [Presentation] 気道上皮細胞と非小細胞肺癌細胞におけるTACEを介したTNFによるEGFRのトランス活性化機序の検討2012

    • Author(s)
      山岡 利光, 村田 泰規, 大木 康成, 楠本 壮二郎, 杉山 智英, 白井 崇生, 中嶌 賢尚, 奥田 健太郎, 大西 司, 大森 亨, 廣瀬 敬, 足立 満
    • Organizer
      日本呼吸器学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] Specific epidermal growth factor receptor autophosphorylation sites promote epithelial cell chemotaxis and restitution2012

    • Author(s)
      山岡利光
    • Organizer
      AACR 2012
    • Place of Presentation
      シカゴ
    • Related Report
      2012 Annual Research Report
  • [Presentation] 気道上皮細胞と非小細胞肺癌細胞におけるTACEを介したTNFによるEGFRのトランス活性化機序の検討2012

    • Author(s)
      山岡利光
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] 気道上皮細胞と非小細胞肺癌細胞におけるTACE/EGFR-リガンドを介したTNFによるEGFRのトランス活性化の機序の検討2011

    • Author(s)
      山岡利光
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 気道上皮細胞と胞肺癌細胞におけるTNFによるEGFRのトランス活性化に寄与するリガンドの同定とアポトーシス制御機構2011

    • Author(s)
      山岡利光
    • Organizer
      日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] 足立満気道上皮細胞と非小細胞肺癌細胞におけるTACE/EGFR-リガンドを介したTNFによるEGFRのトランス活性化の機序検討(TNF transactivates phospho-tyrosine 1068 of EGFR through TACE/EGFR-ligand dependent mechanism)2011

    • Author(s)
      山岡利光, 大木康成, 楠本壮二郎, 杉山智英, 白井崇生, 中嶌賢尚, 奥田健太郎, 廣瀬敬, 大森亨, 大西司
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      大阪
    • Related Report
      2012 Final Research Report
  • [Presentation] TACEを介したEGFRトランス活性化の気道上皮細胞と非小細胞肺癌細胞におけるTNF誘導アポトーシス制御機構の検討2010

    • Author(s)
      山岡利光
    • Organizer
      第69回日本癌学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Transactivation of EGFR/ErbB2 receptor by TNF abrogates TNF-induced apoptosis in bronchial epithelial cells and non-small cell ling cancer2010

    • Author(s)
      山岡利光
    • Organizer
      第101回米国癌学会(AACR)
    • Place of Presentation
      ワシントンDC(米国)
    • Year and Date
      2010-04-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tyrosine site-specific phosphory lation of EGF receptor by TNF-induced transactivation regulates EGFR-ErbB2 intestinal epithelial cell anti-apoptosis2009

    • Author(s)
      山岡利光
    • Organizer
      第100回アメリカ癌学会(AACR)
    • Place of Presentation
      アメリカ(デンバー)
    • Related Report
      2009 Annual Research Report
  • [Presentation] TNFによるEGFRとErbB2のトランス活性化に寄与するEGFRチロシンキナーゼの同定とアポトーシス制御機構2009

    • Author(s)
      山岡利光
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      神奈川県(横浜)
    • Related Report
      2009 Annual Research Report
  • [Book] 癌と化学療法2012

    • Author(s)
      山岡利光
    • Publisher
      癌と化学療法社
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www10.showa-u.ac.jp/~molonco/index/

    • Related Report
      2012 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2019-07-29  

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