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Functional analysis of transcription factors Egr-1 and Egr-3 in VEGF activated endothelial cells

Research Project

Project/Area Number 22700875
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

SUEHIRO Junichi  東京大学, 先端科学技術研究センター, 特任研究員 (80572601)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsVEGF / Egr / ChIP-sea / 血管内皮活性化 / 転写因子Egr / 転写因子NFAT / ChIP-seq
Research Abstract

Transcription factors, Egr-1 and Egr-3, play important roles in VEGF-activated endothelial cells. Here, I performed DNA microarray and ChIP-seq analysis in human umbilical vein endothelial cells(HUVEC) to find new targets. As a result, I found an Egr new target, Rho GTPase 1(RND1). Egr binding sites around RND1 gene located at 25kb upstream of TSS and functioned to enhance transcription. From ChIP-seq and reporter analysis, Egr and NFATc cooperatively contributed to VEGF-mediated RND1 expression. RND1 siRNA inhibited VEGF-mediated cell growth, migration, tube formation, and endothelial barrier function. In B16 melanoma solid tumor model, there were no differences between Egr-1 knockout and wildtype mice, while suppression of Egr-3 inhibited angiogenesis and tumor growth. Taken together, Egr/NFAT-mediated RND1 expression contributed to endothelial activation and there were functional differences between Egr-1 and Egr-3 in vivo.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (21 results)

All 2012 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (10 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Ets family members induce lymph angiogenesis through physical and functional interaction with Prox12011

    • Author(s)
      Yoshimatsu Y, Yamazaki T, Mihira H, Itoh T, Suehiro J, Yuki K, Harada K, Morikawa M, Iwata C, Minami T, Morishita Y, Kodama T, Miyazono K, Watabe T
    • Journal Title

      Cell Sci

      Volume: 124(16) Pages: 2753-62

    • Related Report
      2011 Final Research Report
  • [Journal Article] Epigenetically coordinated GATAT2 binding is necessary for endothelium-specific endomucin expression2011

    • Author(s)
      Kanki Y, Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro J, Wada Y, Ohta Y, Ihara S, Iwanari H, Naito M, Hamakubo T, Aburatani H, Kodama T, Minami T
    • Journal Title

      EMBO J

      Volume: 30 Issue: 13 Pages: 2582-95

    • DOI

      10.1038/emboj.2011.173

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide approaches reveal functional interleukin-4-inducible STAT6 binding to the vascular cell adhesion molecule 1 promoter2011

    • Author(s)
      Tozawa H, Kanki Y, Suehiro J, Tsutsumi S, Kohro T, Wada Y, Aburatani H, Aird WC, Kodama T, Minami T
    • Journal Title

      Mol Cell Biol

      Volume: 31(11) Pages: 2196-209

    • Related Report
      2011 Final Research Report
  • [Journal Article] Ets family members induce lymphangiogenesis through physical and functional interaction with Prox12011

    • Author(s)
      Yoshimatsu Y
    • Journal Title

      Journal of Cell Science

      Volume: 124 Issue: 16 Pages: 2753

    • DOI

      10.1242/jcs.083998

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide approaches reveal functional IL-4 inducible STAT6 binding to the vascular cell adhesion molecule-1 promoter2011

    • Author(s)
      Tozawa H, Kanki Y Suehiro JI, et.al.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 31 Pages: 2196-209

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetically coordinated GATA2 binding is necessary for endothelium specific endomucin expression2011

    • Author(s)
      Kanki y Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro J, et.al.
    • Journal Title

      EMBO J

      Volume: 30 Pages: 2852-95

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Genome-wide analysis revealed NFATc-regulated genes in VEGF-activated endothelial cells2012

    • Author(s)
      Jun-ichi Suehiro, Yasuharu Kanki, Tatsuhiko Kodama, and Takashi Minami
    • Organizer
      Keystone symposium Angiogenesis : Advances in Basic Science and Therapeutic Applications(A3)
    • Place of Presentation
      Snowbird resort
    • Year and Date
      2012-01-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Genome-wide analysis revealed NFATc-regulated genes in VEGF-activated endothelial cells2012

    • Author(s)
      Jun-ichi Suehiro, Yasuharu Kanki, Tatsuhiko Kodama, Takashi Minami
    • Organizer
      Keystone symposium Angiogenesis : Advances in Basic Science and Therapeutic Applications (A3)
    • Place of Presentation
      Snowbird resort (U.S.A)
    • Year and Date
      2012-01-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Genome-wide analysis revealed NFATc-regulated genes in VEGF-activated endothelial cells2011

    • Author(s)
      Jun-ichi Suehiro, Yasuharu Kanki, Tatsuhiko Kodama, and Takashi Minami
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Genome-wide analysis revealed NFATc-regulated genes in VEGF-activated endothelial cells2011

    • Author(s)
      Jun-ichi Suehiro, Yasuharu Kanki, Tatsuhiko Kodama, and Takashi Minami
    • Organizer
      第19回日本血管生物医学会学術集会
    • Place of Presentation
      東京ステーションコンファレンス
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 血管内皮増殖因子による活性化内皮細胞における転写因子NFATc結合部位の網羅的解析2011

    • Author(s)
      末弘淳一、南敬
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Genome-wide analysis of NFATc binding sites in endothelial cells2011

    • Author(s)
      Jun-ichi Suehiro, Tatsuhiko Kodama, and Takashi Minami
    • Organizer
      9th Japan-Korea joint Symposium on Vascular Biology
    • Place of Presentation
      heWest in Chosun Hotel
    • Year and Date
      2011-08-26
    • Related Report
      2011 Final Research Report
  • [Presentation] Genome-wide analysis of NFATc binding sites in endothelial cells2011

    • Author(s)
      Jun-ichi Suehiro, Tatsuhiko Kodama, Takashi Minami
    • Organizer
      9th Japan-Korea joint Symposium on Vascular Biology
    • Place of Presentation
      The Westin Chosun Hotel (Korea)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-32010

    • Author(s)
      末弘淳一、浜窪隆雄、児玉龍彦、William C Aird,南敬
    • Organizer
      第18回日本血管生物医学会学術総会
    • Place of Presentation
      梅田スカイビル
    • Year and Date
      2010-12-01
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 血管内皮細胞増殖因子による内皮活性化での転写因子Egr-3の役割2010

    • Author(s)
      末弘淳一、南敬
    • Organizer
      69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 血管内皮細胞増殖因子による内皮活性化での転写因子Egr-3の役割2010

    • Author(s)
      末弘淳一、南敬
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Book] 血管生物医学事典2011

    • Author(s)
      末弘淳一, 他
    • Total Pages
      500
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report
  • [Book] 血管生物医学事典2011

    • Author(s)
      日本血管生物医学会(末弘淳一, 他)
    • Total Pages
      489
    • Publisher
      朝倉書店
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.vb.rcast.u-tokyo.ac.jp/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.vb.rcast.u-tokyo.ac.jp/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.vb.rcast.u-tokyo.ac.jp/

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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