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Radiation target and mutagenesis in intestinal tumors

Research Project

Project/Area Number 23310036
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionNiigata University

Principal Investigator

KOMINAMI Ryo  新潟大学, 医歯(薬)学総合研究科, 客員研究員 (40133615)

Co-Investigator(Kenkyū-buntansha) MISHIMA Yukio  新潟大学, 医歯学系, 准教授 (30142029)
KATSURAGI Yoshinori  新潟大学, 医歯学系, 助教 (60401759)
OBATA Miki  新潟大学, 医歯学系, 教務職員 (00420307)
広瀬 哲史 (廣瀬 哲史)  新潟大学, 医歯学系, 助教 (10415276)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords電離放射線 / 発がん / 幹細胞 / 大腸がん / 胸腺リンパ腫 / Bcl11b / Bcl11b / 放射線標的細胞 / 発がん母細胞 / 細胞の増殖と消失 / 腸管腫瘍
Research Abstract

Attenuated expression of Bcl11b in Lgr5-expressing intestinal crypt cells promoted regeneration of intestinal epithelial cells after the radiation-induced injury in Lgr5-Cre; Bcl11bflox/+ mice. This suggests that the origin of cells in intestinal tumors, which are enhanced by loss of one Bcl11b allele in Apcmin/+ mice, is Lgr5-expressing cells. It was also demonstrated that Bcl11b functions as a subunit of SWI/SNF chromatin remodeling complex and down-regulates transcription of Wnt/beta-catenin target genes such as c-jun. This suggests that Bcl11b impairment instigates intestinal tumor development at least in part through deregulation of beta-catenin pathway.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (27 results)

All 2014 2013 2012 2011 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (7 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas2014

    • Author(s)
      Okumura K, Saito M, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y
    • Journal Title

      Plos One

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IFN- γ -producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus2014

    • Author(s)
      Shibata K, Yamada H, Nakamura M, Hatano S, Katsuragi Y, Kominami R, Yoshikai Y
    • Journal Title

      J Immunol

      Volume: 192 Pages: 2210-2218

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas.2014

    • Author(s)
      Okumura K, Saito M, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y.
    • Journal Title

      Plos One

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus.2014

    • Author(s)
      Shibata K, Yamada H, Nakamura M, Hatano S, Katsuragi Y, Kominami R, Yoshikai Y.
    • Journal Title

      J. Immunology

      Volume: 192 Issue: 5 Pages: 2210-2218

    • DOI

      10.4049/jimmunol.1302145

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell of origin in radiation-induced premalignant thymocytes in mice conditionally losing one Bcl11b allele2013

    • Author(s)
      Go R, Hirose S, Katsuragi Y, Obata M, Abe M, Mishima Y, Sakimura K, Kominami R
    • Journal Title

      Cancer Sci

      Volume: 104 Pages: 1009-1016

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bcl11b transcription factor plays a role in the maintenance of the ameloblast-progenitors in mouse adult maxillary incisors2013

    • Author(s)
      Katsuragi Y, Anraku J, Nakatomi M, Ida-Yonemochi H, Obata M, Mishima Y, Sakuraba Y, Gondo Y, Kodama Y, Nishikawa A, Takagi R, Ohshima H, Kominami R
    • Journal Title

      Mech Dev

      Volume: 130 Pages: 482-492

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Compound Heterozygosity of the Functionally Null Cdh23v-ngt and Hypomorphic Cdh23ahl/i Alleles Leads to Early-onset Progressive Hearing Loss in Mice2013

    • Author(s)
      Miyasaka Y, Suzuki S, Ohshiba Y, Watanabe K, Sagara Y, Yasuda SP, Matsuoka K, Shitara H, Yonekawa H, Kominami R, Kikkawa Y
    • Journal Title

      Exp Anim

      Volume: 62 Pages: 333-346

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus2013

    • Author(s)
      Tanaka H, Naito T, Muroi S, Seo W, Chihara R, Miyamoto C, Kominami R, Taniuchi I
    • Journal Title

      EMBO J

      Volume: 32 Pages: 1183-1194

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell of origin in radiation-induced premalignant thymocytes in mice conditionally losing one Bcl11b allele.2013

    • Author(s)
      Go R, Hirose S, Katsuragi Y, Obata M, Abe M, Mishima Y, Sakimura K, Kominami R.
    • Journal Title

      Cancer Science

      Volume: 104 Issue: 8 Pages: 1009-1016

    • DOI

      10.1111/cas.12193

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bcl11b transcription factor plays a role in the maintenance of the ameloblast-progenitors in mouse adult maxillary incisors.2013

    • Author(s)
      Katsuragi Y, Anraku J, Nakatomi M, Ida-Yonemochi H, Obata M, Mishima Y, Sakuraba Y, Gondo Y, Kodama Y, Nishikawa A, Takagi R, Ohshima H, Kominami R.
    • Journal Title

      Mechanism and Development

      Volume: 130 Issue: 9-10 Pages: 482-492

    • DOI

      10.1016/j.mod.2013.05.002

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus.2013

    • Author(s)
      Hirokazu Tanaka
    • Journal Title

      EMBO Journal

      Volume: 17 Issue: 8 Pages: 1183-94

    • DOI

      10.1038/emboj.2013.47

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild-derived inbred mouse strain2012

    • Author(s)
      Okumura K, Sato M, Saito M, Miura I, Wakana S, Mao JH, Miyasaka Y, Kominami R, Wakabayashi Y
    • Journal Title

      MSM/Ms. Carcinogenesis

      Volume: 33 Pages: 2260-2268

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impairment in differentiation and cell cycle of thymocytes by loss of a Bcl11b tumor suppressor allele that contributes to leukemogenesis2012

    • Author(s)
      Go, R, Takizawa, K, Hirose, S, Katsuragi, Y, Aoyagi, Y, Mishima, Y, and Kominami, R
    • Journal Title

      Leuk Res

      Volume: 36 Pages: 1035-1040

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of the transcription factor Bcl11b in development and lymphomagenesis2012

    • Author(s)
      Kominami, R
    • Journal Title

      Proc Jpn Acad Ser B

      Volume: 88 Pages: 72-87

    • NAID

      130001924739

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] BCL11B tumor suppressor inhibits HDM2 expression in a p53-dependent manner2012

    • Author(s)
      Obata M, Kominami R, Mishima Y
    • Journal Title

      Cell Signal

      Volume: 24 Pages: 1047-52

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild derived inbred mouse strain, MSM/Ms2012

    • Author(s)
      Okumura K, Sato M, Ikuo M, Wakana S, Mao JH, Miyasaka Y, Kominami R, and Wakabayashi Y.
    • Journal Title

      Carcinogenesis

      Volume: 33 Issue: 11 Pages: 2260-2268

    • DOI

      10.1093/carcin/bgs250

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of the transcription factor Bclllb in development and lymphomagenesis2012

    • Author(s)
      Kominami R
    • Journal Title

      Proc Jpn Acad Ser B

      Volume: 88 Pages: 72-87

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bcl11b heterozygosity leads to age-related hearing loss and degeneration of outer hair cells of the mouse cochlea2011

    • Author(s)
      Okumura H, Miyasaka Y, Morita Y, Nomura T, Mishima Y, Takahashi S, Kominami R
    • Journal Title

      Exp Anim

      Volume: 60 Pages: 355-61

    • NAID

      10029550638

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bcl11b/Ctip2 controls the differentiation of vomeronasal sensory neurons in mice2011

    • Author(s)
      Enomoto T, Ohmoto M, Iwata T, Uno A, Saitou M, Yamaguchi T, Kominami R, Matsumoto I, Hirota J
    • Journal Title

      J Neurosci

      Volume: 31 Pages: 10159-10173

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 放射線発がんにおける発がん母細胞と標的細胞2013

    • Author(s)
      木南 凌, 郷 梨江香, 葛城 美徳, 小幡美貴, 三嶋行雄
    • Organizer
      第55回大会 日本放射線影響学会
    • Place of Presentation
      青森市
    • Year and Date
      2013-10-18
    • Related Report
      2013 Final Research Report
  • [Presentation] 放射線発がんにおける発がん母細胞と標的細胞2013

    • Author(s)
      木南凌、 郷梨江香、葛城美徳、小幡美貴、三嶋行雄
    • Organizer
      日本放射線影響学会
    • Place of Presentation
      青森
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Radiation target cells in thymic lymphomas2012

    • Author(s)
      木南 凌
    • Organizer
      第71回日本がん学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 放射線照射後の腸上皮におけるBcl11bの働き2012

    • Author(s)
      葛城 美徳, 郷 梨江香, 木南 凌
    • Organizer
      第55回大会 日本放射線影響学会
    • Place of Presentation
      仙台市
    • Year and Date
      2012-09-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 放射線照射後の腸上皮におけるBcl11bの働き2012

    • Author(s)
      葛城 美徳
    • Organizer
      第55回大会 日本放射線影響学会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] Radiation target cells in thymic lymphomas2012

    • Author(s)
      木南 凌
    • Organizer
      第71回大会 日本癌学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管腫瘍およびリンパ腫における放射線標的細胞2011

    • Author(s)
      木南凌
    • Organizer
      日本放射線影響学会
    • Place of Presentation
      神戸商工会議所会館(神戸)
    • Year and Date
      2011-11-18
    • Related Report
      2011 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.med.niigata-u.ac.jp/bcl/welcome.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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