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Functional analysis of the Zinc finger E-box binding homeobox 1 (ZEB1/TCF8) gene in the multi-step leukemogenesis of adult T-cell leukemia/lymphoma

Research Project

Project/Area Number 19790344
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionUniversity of Miyazaki

Principal Investigator

NAKAHATA Shingo (NAKAHATA Singo)  University of Miyazaki, 医学部, 助教 (80437938)

Project Period (FY) 2007 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,920,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥720,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥800,000 (Direct Cost: ¥800,000)
Keywords白血病 / 癌 / ウイルス / 遺伝子 / ゲノム
Research Abstract

We identified that TCF8 at 10q11.2 is a candidate tumor-suppressor gene in acute-type adult-T cell leukemia/lymphoma (ATLL). The down-regulation of TCF8 expression by genetic and epigenetic abnormalities in ATLL was associated with resistance to TGF-beta1 treatment, which is one of well-known characteristics of ATL cells. The enforced expression of TCF8 partially restored the responsiveness of ATLL cells to TGF-beta1. Furthermore, TCF8 deficient mice frequently developed invasive CD4^+ T-cell lymphomas in thymus or in ascitic fluids. These findings suggest that TCF8 may become a new therapeutic target for ATLL.

Report

(6 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (28 results)

All 2010 2009 2008 2007

All Journal Article (6 results) (of which Peer Reviewed: 5 results) Presentation (19 results) Book (3 results)

  • [Journal Article] Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to GF-b-mediated growth suppression in adult T-cell leukemia/lympho ma.2010

    • Author(s)
      Nakahata S, Yamazaki S, Nakauchi H, Morishita K.
    • Journal Title

      Oncogene. 29

      Pages: 4157-4169

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to TGF-beta1-mediated growth suppression in adult T-cell leukemia/lymphoma.2010

    • Author(s)
      Nakahata S
    • Journal Title

      Oncogene

      Volume: 29 Pages: 4157-4169

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lympof ihoma.2008

    • Author(s)
      Hidaka T, Nakahata S, Hatakeyama K, Hamasaki M, Yamashita K, Kohno T, Arai Y, Taki T, Nishida K, Okayama A, Asada Y, Yamaguchi R, Tsubouchi H, Yokota J, Taniwaki M, Higashi Y, Morishita K.
    • Journal Title

      Blood. 112

      Pages: 383-393

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma.2008

    • Author(s)
      Hidaka T*, Nakahata S*, Hatakeyama K*, Hamasaki M, Yamashita K, Kohno T, Arai Y, Taki T, Nishida K, Okayama A, Asada Y, Yamaguchi R, Tsubouchi H, Yokota J, Taniwaki M, Higashi Y, Morishita K.
    • Journal Title

      Blood 112

      Pages: 383-393

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma2008

    • Author(s)
      Hidaka T, Nakahata S, Hatakeyama K
    • Journal Title

      Blood 112

      Pages: 383-393

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集「TCF8遺伝子発現抑制による成人T細胞白血病・リンパ腫発症機構」2008

    • Author(s)
      中畑新吾
    • Journal Title

      血液フロンティア医薬ジャーナル社(大阪) 18

      Pages: 65-72

    • Related Report
      2008 Annual Research Report
  • [Presentation] Promoter methylation and down-regulation of ZEB1 are associated with low expression of CDKN1A in ATL cells2010

    • Author(s)
      中畑新吾
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 成人T細胞白血病細胞におけるCDKN1A遺伝子の転写はプロモーターのメチル化とZEB1 発現低下により抑制される2010

    • Author(s)
      中畑新吾
    • Organizer
      第73回日本血液学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2010-09-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 成人T細胞白血病細胞におけるCDKN1A遺伝子の転写はプロモーターのメチル化とZEB1発現低下により抑制される2010

    • Author(s)
      中畑新吾
    • Organizer
      第73回日本血液学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Promoter methytation and down-regulation of ZEB1 are associated with low expression of CDKN1A in ATL cells2010

    • Author(s)
      中畑新吾
    • 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
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] ATL細胞におけるCDKN1A遺伝子の転写はプロモーターのメチル化とZEB1発現低下により抑制される2010

    • Author(s)
      中畑新吾
    • Organizer
      第3回HTLV-1研究会・合同斑会議
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2010-08-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 成人T細胞白血病リンパ腫(ATLL)におけるZEB1/TCF8転写抑制はCCNG2及びCDKN1Aの転写抑制をもたらす。2009

    • Author(s)
      中畑新吾
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Down-regulation of CDKN1A transcription by ZEB1/TCF8 inactivation in adult T-cell leukemia.2009

    • Author(s)
      中畑新吾
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] ATLLにおけるZEB1転写抑制はCCNG2及びCDKN1Aの転写抑制を介した細胞増殖をきたす2009

    • Author(s)
      中畑新吾
    • Organizer
      第2回HTLV-1研究会・合同斑会議
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2009-08-30
    • Related Report
      2010 Final Research Report 2009 Self-evaluation Report
  • [Presentation] ATLLにおけるZEB1転写抑制はCCNG2及びCDKN1Aの転写抑制を介した細胞増殖すきたす。2009

    • Author(s)
      中畑新吾
    • Organizer
      第2回HTLV-1研究会・合同斑会議
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2009-08-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] ATLLのTGF-betal不能性はゲノム異常によるTCF8発現低下とSMAD7高発現によりもたらされる2008

    • Author(s)
      中畑新吾
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] TCF8 expression overcomes the resistance to TGFbetal-induced growth in hibition by Smad7 overexpression in ATL2008

    • Author(s)
      中畑新吾
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] TCF8はSmad7を抑制しATLのTGF-beta1不能性を解除する2008

    • Author(s)
      中畑新吾
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-10-12
    • Related Report
      2010 Final Research Report 2009 Self-evaluation Report
  • [Presentation] TCF8はSmad7を抑制しATLのTGF-betal不能性を解除する2008

    • Author(s)
      中畑新吾
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-10-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] TCF8遺伝子発現低下によるATLL発症機構の解析2008

    • Author(s)
      中畑新吾
    • Organizer
      第1回HTLV-1研究会・合同斑会議
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2008-08-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] TCF8遺伝子発現低下によるATLL発症機構の解析2007

    • Author(s)
      中畑新吾
    • Organizer
      第30回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] TCF8遺伝子発現低下によるATLL発症機構の解析2007

    • Author(s)
      中畑新吾
    • Organizer
      第69回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Downregulation of TCF8 is involved in ATLL development by the escape from TGF-beta1 during T cell differentiation.2007

    • Author(s)
      中畑新吾
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横
    • Year and Date
      2007-10-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Downregulation of TCF8 is involved in ATLL development by the escape from TGF-beta1 during T cell differentiation.2007

    • Author(s)
      中畑新吾
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-10-05
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] TCF8遺伝子の発現低下はT細胞分化過程におけるTCF-betalの選択を回避しATLLの発症に関与する2007

    • Author(s)
      中畑新吾
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Book] Annual Review 血液(ATLの発症機構)2010

    • Author(s)
      中畑新吾、森下和広
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] 血液フロンティ18巻(TCF8遺伝子発現抑制による成人T細胞白血病・リンパ腫発症機構)2008

    • Author(s)
      中畑新吾、森下和広
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Final Research Report
  • [Book] TCF8遺伝子発現抑制による成人T細胞白血病・リンパ腫発症機構2008

    • Author(s)
      中畑新吾, 森下和広
    • Publisher
      医薬ジャーナル社
    • Related Report
      2009 Self-evaluation Report

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

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