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Expression analysis of DoK-1, Dok-2 and Dok-3 genes in mice expressing Tax, a human T-cell leukemia virus type 1 oncoprotein

Research Project

Project/Area Number 15K06806
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionRakuno Gakuen University

Principal Investigator

Ohsugi Takeo  酪農学園大学, 獣医学群, 教授 (00211102)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHTLV-1 / Tax / 成人T細胞白血病 / Dok-1 / Dok-2 / Dok-3 / 遺伝子改変マウス / DOK1 / DOK2 / DOK3 / DOK1 / Dok1 / Dok2 / Dok3
Outline of Final Research Achievements

Human T-cell leukemia virus type 1 (HTLV-1) can cause adult T-cell leukemia/lymphoma (ATL). The Tax protein encoded by HTLV-1 appears to be a key element in the early stage of ATL development. We examined the expression of the downstream of tyrosine kinase (Dok) family members Dok-1, Dok-2 and Dok-3, recently reported to be tumor suppressors, in HTLV-1-infected T cells and transgenic mice expressing the tax gene. Dok-2 and Dok-3 expression was significantly reduced in HTLV-1-infected T cells compared with their expression in uninfected T cells, and the expression of Dok-3 was reduced by the induction of Tax expression in T cells. The transgenic mice showed low expression of Dok-1, Dok-2 and Dok-3 in mice with T cell leukemia. Mice showed low Dok-2 expression at 5-6 months of age before disease onset. These results suggest that downregulation of Dok-2 and Dok-3 by the expression of the viral tax gene is the first step in the development of ATL.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Effects of expressing human T-cell leukemia virus type 1 (HTLV-I) oncoprotein Tax on <i>DOK1</i>, <i>DOK2</i> and <i>DOK3</i> gene expression in mice2017

    • Author(s)
      Ohsugi, T.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 79 Issue: 5 Pages: 935-938

    • DOI

      10.1292/jvms.17-0034

    • NAID

      130005665593

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of DOK1, 2, and 3 genes in HTLV-1-infected T cells.2016

    • Author(s)
      Ohsugi, T., Wakamiya, M., Morikawa, S. and Fujita, M.
    • Journal Title

      Acta Virologica

      Volume: 60 Issue: 02 Pages: 211-213

    • DOI

      10.4149/av_2016_02_211

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of a combination of alfaxalone with medetomidine and butorphanol for inducing surgical anesthesia in laboratory mice2016

    • Author(s)
      Higuchi, S., Yamada, R., Hashimoto, A., Miyoshi, K.,Yamashita, K. and Ohsugi, T.
    • Journal Title

      Japanese Journal of Veterinary Research

      Volume: 64 Issue: 2 Pages: 131-139

    • DOI

      10.14943/jjvr.64.2.131

    • NAID

      120005763158

    • ISSN
      0047-1917
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of a combination of alfaxalone with medetomidine and butorphanol for inducing surgical anesthesia in laboratory mice2016

    • Author(s)
      Higuchi, S., Yamada, R., Hashimoto, A., Miyoshi, Yamashita, K. and Ohsugi, T.
    • Journal Title

      Japanese Journal of Veterinary Research

      Volume: -

    • NAID

      120005763158

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of DOK1, 2, and 3 genes in HTLV-1-infected T cells2016

    • Author(s)
      Ohsugi, T., Wakamiya, M., Morikawa, S. and Fujita, M.
    • Journal Title

      Acta Virologica

      Volume: -

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 成人T細胞白血病(ATL)治療の最前線-抗CCR4抗体の憂鬱-2015

    • Author(s)
      大杉剛生
    • Journal Title

      日本ウイルス学会北海道支部報

      Volume: 46 Pages: 2-6

    • Related Report
      2015 Research-status Report
  • [Presentation] アルファキサロンを用いた新規混合麻酔薬の各マウス系統での評価2018

    • Author(s)
      塚本依子、山田典英、三好健二郎、山下和人、大杉剛生
    • Organizer
      第65回日本実験動物学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development and molecular analysis of synthetic lethality by targeting EZH1/2 in ATL and HTLV-1-infected cells.2017

    • Author(s)
      Yamagishi, M., Hori, M., Fujiwara, D., Honma, D., Adachi, N., Ohsugi, T., Nakano, K., Nakashima, M., Kobayashi, S., Iwanaga, M., Utsunomiya, A., Tanaka, Y., Okada, S., Tsukasaki, K., Toninai, K., Araki, K., Watanabe, T. and Uchimaru, K.
    • Organizer
      18th International Conference on Human Retrovirology HTLV and Related Viruses
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京都)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tamoxifen inhibits the infiltration of human T-cell leukemia virus type 1-infected cells into organs in a mouse model of adult T-cell leukemia.2017

    • Author(s)
      Tanaka, Y., Kozuka, T., Yamagishi, M., Hirose, T., Nagano, Y., Nishii, R., Kitamura, H., Takehana, K., Watanabe, T. and Ohsugi, T.
    • Organizer
      18th International Conference on Human Retrovirology HTLV and Related Viruses
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京都)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] アルファキサロン、メデトミジン、ブトルファノール三種混合麻酔薬の実験用マウスにおける性差および系統差2017

    • Author(s)
      山田典英、塚本依子、山田 陸、三好健二郎、山下和人、大杉剛生
    • Organizer
      第64回日本実験動物学会総会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] 成人T細胞白血病(ATL)モデルマウスにおけるタモキシフェンの効果2017

    • Author(s)
      長野佑祐、西井里衣、小塚友樹、田中雄三、大杉剛生
    • Organizer
      第14回北海道実験動物研究会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] EZH1/2阻害による悪性リンパ腫のエピゲノム制御2017

    • Author(s)
      山岸 誠、堀 真琴、藤川 大、本間 大輔、安達 宣明、大杉 剛生、中野 和民、中島 誠 、小林 誠一郎、岩永 正子 、宇都宮 與、岡田 誠治、塚崎 邦弘、飛内 賢正、荒木 一司、渡邉 俊樹、内丸 薫
    • Organizer
      第79回日本血液学学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] タモキシフェンによるHTLV-1感染細胞増殖抑制2017

    • Author(s)
      大杉剛生、長野佑祐、田中 雄三、小塚友喜、西井里衣、山岸 誠、渡邉俊樹
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アルファキサロン、メデトミジン、ブトルファノール三種混合麻酔薬のマウスへの応用2016

    • Author(s)
      山田 陸、樋口翔太、橋本麻美、三好健二郎、山下和人、大杉剛生
    • Organizer
      第63回日本実験動物学会総会
    • Place of Presentation
      ミューザ川崎シンフォニーホール(神奈川県・川崎市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Presentation] 成人T細胞白血病のモデルマウスの進展2015

    • Author(s)
      大杉剛生
    • Organizer
      第12回北海道実験動物研究会
    • Place of Presentation
      北海道大学医学部講義棟(北海道・札幌市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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