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Identification of the genes involved in the tumorigenesis and spontaneous regression in neuroblastoma model mice

Research Project

Project/Area Number 24590377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

KISHIDA Satoshi  名古屋大学, 医学(系)研究科(研究院), 助教 (20402563)

Co-Investigator(Kenkyū-buntansha) KADOMATSU Kenji  名古屋大学, 大学院医学系研究科, 教授 (80204519)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経芽腫 / モデルマウス / 自然退縮 / トランスジェニックマウス / 神経堤 / 神経芽種 / 次世代シーケンサー / がん幹細胞
Outline of Final Research Achievements

In this research, we tried to identify the genes involved in the tumorigenesis of neuroblastoma, one of the malignant pediatric solid tumors. Based on our comprehensive data acquired from MYCN transgenic (Tg) mice, we identified two genes, NeuroD1 and H1FX. Both were highly expressed in the early lesions of MYCN Tg mice. We showed that NeuroD1 directly induced the transcription of ALK, an important predisposeition gene in neuroblastoma. NeuroD1-ALK axis promotes the proliferation of neuroblastoma cells. On the other hand, H1FX seems to be involved in the early development of sympathetic neurons. H1FX was highly and specifically expressed in totally undifferentiated neuroblast in vivo, and disappeared after differentiation. Interestingly, the expression of H1FX in patients was closely correlated with that of Midkine, a growth factor involved in neuroblastoma tumorigenesis. H1FX could be a target of midkine signaling.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (5 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] The nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation.2015

    • Author(s)
      Nakaguro M, Kiyonari S, Kishida S, Cao D, Murakami-Tonami Y, Ichikawa H, Takeuchi I, Nakamura S, Kadomatsu K
    • Journal Title

      Cancer Science

      Volume: 106 Issue: 3 Pages: 237-243

    • DOI

      10.1111/cas.12598

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NeuroD1 promotes neuroblastoma cell growth by inducing the expression of ALK.2015

    • Author(s)
      Lu F, Kishida S, Mu P, Huang P, Cao D, Tsubota S, Kadomatsu K.
    • Journal Title

      Cancer Science

      Volume: in press Issue: 4 Pages: 390-396

    • DOI

      10.1111/cas.12628

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.2014

    • Author(s)
      Murakami-Tonami Y, Kishida S, Takeuchi I, Katou Y, Maris JM, Ichikawa H, Kondo Y, Sekido Y, Shirahige K, Murakami H, Kadomatsu K.
    • Journal Title

      Cell Cycle.

      Volume: 13 Issue: 7 Pages: 1115-1131

    • DOI

      10.4161/cc.27983

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model.2014

    • Author(s)
      Cao D, Kishida S, Huang P, Mu P, Tsubota S, Mizuno M, Kadomatsu K.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 1 Pages: 1-8

    • DOI

      10.1371/journal.pone.0086813

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of midkine in cardiovascular disease2014

    • Author(s)
      Kadomatsu K, Bencsik P, Görbe A, Csonka C, Sakamoto K, Kishida S, Ferdinandy P
    • Journal Title

      Br J Pharmacol

      Volume: 171(4) Issue: 4 Pages: 936-944

    • DOI

      10.1111/bph.12537

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of midkine in neuroblastoma tumourigenesis2014

    • Author(s)
      Kishida S, Kadomatsu K
    • Journal Title

      Br J Pharmacol

      Volume: 171(4) Issue: 4 Pages: 896-904

    • DOI

      10.1111/bph.12442

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.2013

    • Author(s)
      Hasan MK, Nafady A, Takatori A, Kishida S, Ohira M, Suenaga Y, Hossain S, Akter J, Ogura A, Nakamura Y, Kadomatsu K, Nakagawara A.
    • Journal Title

      Sci Rep

      Volume: 3 Issue: 1 Pages: 3450-3450

    • DOI

      10.1038/srep03450

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Midkine promotes neuroblastoma through Notch2 signaling2013

    • Author(s)
      Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, Onishi A, Nakamura Y, Kadomatsu K
    • Journal Title

      Cancer Res

      Volume: 73(4) Issue: 4 Pages: 318-327

    • DOI

      10.1158/0008-5472.can-12-3070

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] The RNA Aptamer against Midkine Suppresses Neuroblastoma Xenograft Growth by Attenuating Midkine-Notch2 Pathway.2014

    • Author(s)
      岸田聡
    • Organizer
      Advances in Neuroblastoma Research 2014 (ANR2014)
    • Place of Presentation
      Cologne, Germany
    • Year and Date
      2014-05-13 – 2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNA aptamer and monoclonal antibody-mediated targeting of midkine against neuroblastoma2014

    • Author(s)
      岸田聡
    • Organizer
      The Third Midkine Symposium
    • Place of Presentation
      京都府京都市、京都ホテルオークラ
    • Year and Date
      2014-04-21 – 2014-04-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Midkine promotes neuroblastoma through Notch2 signaling in model mice2013

    • Author(s)
      Satoshi Kishida, Ping Mu, Shin Miyakawa, Masatoshi Fujiwara, Tomoyuki Abe, Kazuma Sakamoto, Yoshikazu Nakamura, Kenji Kadomatsu
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] 難治性小児がん神経芽腫の治療に向けた抗MK抗体の開発2013

    • Author(s)
      岸田聡
    • Organizer
      平成25年度 中部地区医療・バイオ系シーズ発表会
    • Place of Presentation
      ウィンクあいち、名古屋市
    • Related Report
      2013 Research-status Report
  • [Presentation] The growth factor Midkine plays a critical role in the tumorigenesis of neuroblastoma via Notch2 signaling2012

    • Author(s)
      Satoshi Kishida
    • Organizer
      Advances in Neuroblastoma Research 2012 (ANR2012)
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2012 Research-status Report
  • [Book] Sugar Chains2015

    • Author(s)
      Nobuko Hosokawa, Tadashi Suzuki, Morihisa Fujita, Xiao-Dong Gao, Taroh Kinoshita, Masakazu Nagafuku, Jin-ichi Inokuchi, Koichi Furukawa, Yasuyuki Matsumoto, Qing Zhang, Keiko Furukawa, Tadanobu Takahashi, Takashi Suzuki, Hiroaki Tateno, Jun Hirabayashi, Tadahisa Mikami, Satoshi Kishida, Kenji Kadomatsu et al.
    • Total Pages
      287
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトミッドカインに対するモノクローナル抗体2013

    • Inventor(s)
      門松健治、岸田聡、小野健一郎、八木香澄
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-07-30
    • Related Report
      2013 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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