Radiation target and mutagenesis in intestinal tumors

• Project/Area Number: 23310036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Niigata 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: ¥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.

Research Products

• [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)
  • 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 Immunol Volume: 192 Pages: 2210-2218
  • 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
  • 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
  • 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 Sci Volume: 104 Pages: 1009-1016
  • 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: Mech Dev Volume: 130 Pages: 482-492
  • 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 Mice (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus (2013)
  • 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
  • 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
  • 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
  • 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
  • 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 (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Impairment in differentiation and cell cycle of thymocytes by loss of a Bcl11b tumor suppressor allele that contributes to leukemogenesis (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Role of the transcription factor Bcl11b in development and lymphomagenesis (2012)
  • Author(s): Kominami, R
  • Journal Title: Proc Jpn Acad Ser B Volume: 88 Pages: 72-87
  • NAID: 130001924739
  • Peer Reviewed
• [Journal Article] BCL11B tumor suppressor inhibits HDM2 expression in a p53-dependent manner (2012)
  • Author(s): Obata M, Kominami R, Mishima Y
  • Journal Title: Cell Signal Volume: 24 Pages: 1047-52
  • 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/Ms (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Role of the transcription factor Bclllb in development and lymphomagenesis (2012)
  • Author(s): Kominami R
  • Journal Title: Proc Jpn Acad Ser B Volume: 88 Pages: 72-87
  • Peer Reviewed
• [Journal Article] Bcl11b heterozygosity leads to age-related hearing loss and degeneration of outer hair cells of the mouse cochlea (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Bcl11b/Ctip2 controls the differentiation of vomeronasal sensory neurons in mice (2011)
  • 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
  • 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
• [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
  • Invited
• [Presentation] Radiation target cells in thymic lymphomas (2012)
  • 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
• [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
• [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
• [Presentation] Radiation target cells in thymic lymphomas (2012)
  • Author(s): 木南 凌
  • Organizer: 第71回大会 日本癌学会総会
  • Place of Presentation: 札幌
• [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
• [Remarks] 研究室ホームページ
  • URL: http://www.med.niigata-u.ac.jp/bcl/welcome.html