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Screening of polycomb Bmi1 targets for development of Cancer Stem Cell-targeted therapy for neuroblastoma

Research Project

Project/Area Number 21591377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

KAMIJO Takehiko  千葉県がんセンター(研究所), 発がん研究グループ, 部長 (90262708)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsBmi1 / 小児腫瘍 / ポリコーム / がん幹細胞 / BMI1 / アポトーシス
Research Abstract

We clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bb and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bb and TSLC1 are direct targets of Bmi1 in NB cells.
Further comprehensive molecular analysis indicated that RUNX3 appears to be a target of Bmi1 and its transcription was suppressed by Bmi1 in several malignancies, including neuroblastoma.
Analysis of the molecular mechanism of Bmi1-knockdown-induced apoptosis clarified that DNA damage induced by Bmi1 knockdown has an important role. This apoptosis is dependent on p53 and/or p73 and accompanied by production of reactive oxygen species. Furthermore, we studied the role of the other polycomb group molecules in the Bmi1-knockdown-induced apoptotic cell death.

Report

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

    (51 results)

All 2012 2011 2010 2009 Other

All Journal Article (22 results) (of which Peer Reviewed: 12 results) Presentation (20 results) Book (5 results) Remarks (4 results)

  • [Journal Article] Role of stemness-related molecules in neuroblastoma2012

    • Author(s)
      Kamijo T
    • Journal Title

      Pediatric Research

      Volume: 71巻 Pages: 511-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD133 suppresses neuroblastoma cell differentiation via signal pathway-modification2011

    • Author(s)
      Takenobu H, Shimozato O, Nakamura T, Ochiai H, Yamaguchi Y, Ohira M, Nakagawara A, Kamijo T
    • Journal Title

      ONCOGENE

      Volume: 30(1) Pages: 97-105

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mammalian Polycomblike Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate Polycomb activity at both the Hox gene cluster and at Cdkn2a genes2011

    • Author(s)
      Li X, Isono K, Yamada D, Endo TA, Endoh M, Shinga J, Koseki YM, Otte AP, Casanova M, Kitamura M, Kamijo T, Sharif J, Ohara O, Toyada T, Bernstein BE, Brockdorff N and Koseki H
    • Journal Title

      Mol Cell Biol

      Volume: 31(2) Pages: 351-64

    • Related Report
      2011 Final Research Report
  • [Journal Article] Bmi1 regulates cell fate via tumor suppressor WWOX repression in small cell lung cancer cells2011

    • Author(s)
      Kimura M, Takenobu H, Akita N, Nakazawa A, Ochiai H, Shimozato O, Fujimura YI, Koseki H, Yoshino I, Kimura H, Nakagawara A, Kamijo T
    • Journal Title

      Cancer Sci

      Volume: 102(5) Pages: 983-990

    • NAID

      10029293384

    • Related Report
      2011 Final Research Report
  • [Journal Article] Regulation of the MDM2-P53 Pathway and Tumor Growth by PICT1/GLTSCR2 via Nucleolar RPL112011

    • Author(s)
      Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wang J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Tomohiko Maehama T, Mori M, and Suzuki A
    • Journal Title

      Nat Med

      Volume: 17(8) Pages: 944-51

    • Related Report
      2011 Final Research Report
  • [Journal Article] CD133 suppresses neuroblastoma cell differentiation via signal pathway-modification2011

    • Author(s)
      Takenobu H, Shimozato O, Nakamura T, Ochiai H, Yamaguchi Y, Ohira M, Nakagawara A, Kamijo T (corresponding author)
    • Journal Title

      ONCOGENE

      Volume: 30巻 Pages: 97-105

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian Polycomblike Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate Polycomb activity at both the Hox gene cluster and at Cdkn2a genes2011

    • Author(s)
      Li X, Isono K, Yamada D, Endo TA, Endoh M, Shinga J, Koseki YM, Otte AP, Casanova M, Kitamura M, Kamijo T, Sharif J, Ohara O, Toyada T, Bernstein BE, Brockdorff N, Koseki H
    • Journal Title

      Mol Cell Biol

      Volume: 31 Pages: 351-64

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bmi1 regulates cell fate via tumor suppressor WWOX repression in small cell lung cancer cells2011

    • Author(s)
      Kimura M, Takenobu H, Akita N, Nakazawa A, Ochiai H, Shimozato O, Fujimura YI, Koseki H, Yoshino I, Kimura H, Nakagawara A, Kamijo T (corresponding author)
    • Journal Title

      Cancer Science

      Volume: 102巻 Pages: 983-990

    • NAID

      10029293384

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the MDM2-P53 Pathway and Tumor Growth by PICT1/GLTSCR2 via Nucleolar RPL112011

    • Author(s)
      Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hatnada K, Itoh B, Wang J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Tomohiko Maehama T, Mori M, Suzuki A
    • Journal Title

      Nat Med

      Volume: 17巻 Pages: 944-51

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disappearance of Minimal Residual Disease After the Early Withdrawal of Immunosuppressants in a Patient With Juvenile Myelomonocytic Leukemia2011

    • Author(s)
      Yanagisawa R, Matsuda K, Sakashita K, Nakazawa Y, Tanaka M, Saito S, Yoshikawa K, Kamijo T, Shiohara M, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 56巻 Pages: 501-2

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bmi1 is a MYCN target gene and regulates tumorigenesis via repression of KIF1B・and TSLC1 in neuroblastoma2010

    • Author(s)
      Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura K, Ohira M, Okimoto Y, Fujimura Y, Koseki H, Kohno Y, Nakagawara A, Kamijo T
    • Journal Title

      ONCOGENE

      Volume: 29(18) Pages: 2681-90

    • Related Report
      2011 Final Research Report
  • [Journal Article] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma2010

    • Author(s)
      Iwata S, Takenobu H, Kageyama H, Koseki H, Ishii T, Nakazawa A, Tatezaki SI, Nakagawara A, Kamijo T
    • Journal Title

      Cancer Sci

      Volume: 101(7) Pages: 1646-52

    • NAID

      10026594687

    • Related Report
      2011 Final Research Report
  • [Journal Article] HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53/p73-dependent manner in neuroblastoma2010

    • Author(s)
      Shi Y, Taenobu H, Kurata K, Yamaguchi Y, Yanagisawa R, Ohira M, Koike K, Nakagawara A, Jiang LL, Kamijo T
    • Journal Title

      European J of Cancer

      Volume: 46(12) Pages: 2324-34

    • Related Report
      2011 Final Research Report
  • [Journal Article] Reevaluation of trkA expression as a biological marker of neuroblastoma by high-sensitivity expression analysis-a study of 106 primary neuroblastomas treated in a single institute2010

    • Author(s)
      Hishiki T, Saito T, Terui K, Sato Y, Takenouchi A, Yahata E, Ono S, Nakagawara A, Kamijo T, Nakamura Y, Matsunaga T, Yoshida H
    • Journal Title

      J Pediatr Surg

      Volume: 45(12) Pages: 2293-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma2010

    • Author(s)
      Iwata S, Kamijo T, et al
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 1646-1652

    • NAID

      10026594687

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bmi1 is a MYCN target gene and regulates tumorigenesis via repression of KIF1Bβ and TSLC1 in neuroblastoma.2010

    • Author(s)
      Ochiai H, Kamijo T, et al
    • Journal Title

      Oncogene

      Volume: 29 Pages: 2681-2690

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HDM2 impairs Noxa transcription and affects apoptotic cell death in ap53/p73-dependent manner in neuroblastoma2010

    • Author(s)
      Shi Y, Kamijo T, et al
    • Journal Title

      European J of Cancer

      Volume: 46 Pages: 2324-2334

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma2010

    • Author(s)
      Iwata S, Kamijo T, et al
    • Journal Title

      Cancer Science (in press)

    • NAID

      10026594687

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bmil is a MYCN target gene and regulates tumorigenesis via repression of KIF1Bβ and TSLC1 in neuroblastoma2010

    • Author(s)
      Ochiai H, Kamijo T, et al
    • Journal Title

      Oncogene (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plk1 regulates liver tumor cell death by phosphorylation of TAp632009

    • Author(s)
      Komatsu S, Takenobu H, Ozaki T, Ando K, Koida N, Suenaga Y, Ichikawa T, Hishiki T, Chiba T, Iwama A, Yoshida H, Ohnuma N, Nakagawara A, Kamijo T
    • Journal Title

      Oncogene

      Volume: 28(41) Pages: 3631-41

    • Related Report
      2011 Final Research Report
  • [Journal Article] TBP(TATA-binding Protein)-like Protein(TLP) Is Engaged in Etoposide-induced Apoptosis Through Transcriptional Activation of HumanTAp63 Gene2009

    • Author(s)
      Suenaga Y, Ozaki T, Tanaka Y, Bu Y, Kamijo T, Tokuhisa T, Nakagawara A, Tamura TA
    • Journal Title

      J Biol Chem

      Volume: 284(51) Pages: 35433-40

    • Related Report
      2011 Final Research Report
  • [Journal Article] Plk1 regulates liver tumor cell death by phosphorylation of TAp632009

    • Author(s)
      Komatsu S, Kamijo T, et al
    • Journal Title

      Oncogene 28巻

      Pages: 3631-41

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 神経芽腫/脳腫瘍スフェア特異的なCD133発現調節機構2011

    • Author(s)
      竹信尚典, 下里修, 秋田直洋, 山口陽子, 吉田早哉香, 落合秀匡, 大平美紀, 中川原章, 上條岳彦
    • Organizer
      第53回日本小児血液・がん学会
    • Place of Presentation
      前橋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] BMI1発現抑制による難治性神経芽腫の細胞死・分化誘導療法の開発2011

    • Author(s)
      秋田直洋, 竹信尚典, 落合秀匡, 永瀬浩喜, 中川原章, 上條岳彦
    • Organizer
      第53回日本小児血液・がん学会
    • Place of Presentation
      前橋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経芽腫の予後に相関するマイクロRNA発現パターンの検索2011

    • Author(s)
      大平美紀, 磯貝恵理子, 中村洋子, 上條岳彦, 中川原章
    • Organizer
      第53回日本小児血液・がん学会
    • Place of Presentation
      前橋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経芽腫におけるゲノム分類と国際病理分類(INPC)との比較検討2011

    • Author(s)
      岡松千都子, 中澤温子, 大平美紀, 上條岳彦, 中川原章
    • Organizer
      第53回日本小児血液・がん学会
    • Place of Presentation
      前橋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経芽腫の生物学2011

    • Author(s)
      上條岳彦
    • Organizer
      第53回日本小児血液・がん学会
    • Place of Presentation
      前橋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] Shf, a novel adaptor protein, inhibits ALK-mediated suvival signals in neuroblastoma2011

    • Author(s)
      Daisuke Takagi, Yasutoshi Tatsumi, Atsushi Takatori, Miki Ohira, Takehiko Kamijo, Satoshi Kondo, Akira Nakagawara
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Expresion Changes of cancer stem-like cell marker in XRCC4 deficient human colon cancer cells after X-ray irradiation2011

    • Author(s)
      Sei Sai, Kazuhiko Oonishi, Masahiko Mori, Takehiko Kamijo, Shigeru Yamada, Tadashi Kamada
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Acquired multi-drug resistance in human colon cancer cells by sphere formation2011

    • Author(s)
      Kumiko Nakashima, Osamu Shimozato, Hisanori Takenobu, Toshinori Ozaki, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tumor sphere specific CD133 regulation in neuroblastoma2011

    • Author(s)
      Hisanori Takenobu, Osamu Shimozato, Nobuhiro Akita, Yohko Yamaguchi, Sayaka Yoshida, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] CD133 plays roles in keeping the undifferentiated status of human colon cancer cells via PI3K/AKT activation2011

    • Author(s)
      Osamu Shimozato, Kumiko Nakashima, Hisanori Takenobu, Toshinori Ozaki, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] BMI1 regulates neuroblastoma apoptotic cell death and differentiation2011

    • Author(s)
      Nobuhiro Akita, Hisanori Takenobu, Hiroki Nagase, Takehiko Kamijo
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identificerion of prognosis-related miRNA expression profiles in neuroblastoma2011

    • Author(s)
      Miki Ohira, Eriko Isogai, Yohko Nakamura, Takehiko Kamijo, Akira Nakagawara
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Genomic Approach to the prediction of chemotherapeutic sensitivity in osteosarcoma2011

    • Author(s)
      Shintaro Iwata, Miki Ohira, Takehiko Kamijo, Tsukasa Yonemoto, Takeshi Ishii, Shin-ichiro Tatezaki, Akira Nakagawara
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] RUNX2 is involved in p53-mediated DNA damage response2011

    • Author(s)
      Natsumi Kubo, Dan Wu, Akira Nakagawara, Takehiko Kamijo, Toshinori Ozaki
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] DMAP1 works as a novel 1p tumor suppressor via ATM/p53 activation2011

    • Author(s)
      Yohko Yamaguchi, Hisanori Takenobu, Sayaka Yoshida, Miki Ohira, Atsushi Iwama, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] MDM2 impairs NOXA transcription and affects apoptotic cell death in a p53/p73-dependent manner in neuroblastoma2011

    • Author(s)
      Yun Shi, Hisanori Takenobu, Kenji Kurata, Yohko Yamaguchi, Ken-ichi Koike, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      The 5th International p63/p73 Workshop
    • Place of Presentation
      リヨン(フランス)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 幹細胞マーカーCD133は細胞内シグナル活性化を介して神経芽腫の増殖と分化を制御する2011

    • Author(s)
      竹信尚典, 上條岳彦
    • Organizer
      第116回小児血液腫瘍懇話会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] Bmi1 regulates cell fate via tumor suppressor WWOX repression in small cell lung cancer cells2011

    • Author(s)
      Masaki Kimura, Hisanori Takenobu, Nobuhiro Akita, Osamu Shimozato, Hideki Kimura, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      AACR 102nd Annual Meeting 2011
    • Place of Presentation
      フロリダ(アメリカ)
    • Related Report
      2011 Annual Research Report
  • [Presentation] BMI1は神経芽腫においてCD133発現を促進し、細胞死・分化を制御する2010

    • Author(s)
      秋田直洋、竹信尚典、落合秀匡、中川原章、上條岳彦
    • Organizer
      第69回日本癌学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 固形腫瘍におけるがん幹細胞2009

    • Author(s)
      上條岳彦
    • Organizer
      第25回小児がん・第51回小児血液学会
    • Place of Presentation
      東京ベイホテル東急
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Book] Neuroblastoma : Role of MYCN/Bmi1 Pathway in Neuroblastoma. Pediatric Cancer, Volume 1, Neuroblastoma2012

    • Author(s)
      Takehiko Kamijo
    • Total Pages
      280
    • Publisher
      Springer Science+Business Media B.V.
    • Related Report
      2011 Annual Research Report
  • [Book] がん組織バンクとその応用研究2010

    • Author(s)
      上條岳彦、中村洋子、大平美紀、中川原章
    • Publisher
      永井書店
    • Related Report
      2011 Final Research Report
  • [Book] 癌診療ハンドブック改訂第2版2010

    • Author(s)
      上條岳彦、中村洋子、大平美紀、中川原章
    • Total Pages
      135
    • Publisher
      永井書店
    • Related Report
      2010 Annual Research Report
  • [Book] 血液・腫瘍性疾患神経芽腫2009

    • Author(s)
      上條岳彦
    • Publisher
      東京医学社
    • Related Report
      2011 Final Research Report
  • [Book] 【小児疾患診療のための病態生理】41(増刊)2009

    • Author(s)
      上條岳彦
    • Total Pages
      1384
    • Publisher
      小児内科
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/organization/005.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/organization/005.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/index.html

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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