Host factors and genetic mutations in radiation carcinogenesis

2009 Fiscal Year Final Research Report

• Project/Area Number: 18201009
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Niigata University
• Principal Investigator: KOMINAMI Ryo Niigata University, 医歯学系, 教授 (40133615)
• Co-Investigator(Kenkyū-buntansha): MISHIMA Yukio 新潟大学, 医歯学系, 准教授 (30166003) ; KTURAGI Yshinori 新潟大学, 医歯学系, 助教 (60401759) ; HIROSE Stoshi 新潟大学, 医歯学系, 助教 (10415276) ; OBATA Miki 新潟大学, 医歯学系, 教務職員 (00420307)
• Project Period (FY): 2006 – 2009
• Keywords: 発がん感受性 / 電離放射線影響 / 前リンパ腫細胞・腸管腫瘍 / Bcl11b遺伝子

Research Abstract

放射線照射は胸腺細胞の減少と萎縮をもたらすが、その萎縮した胸腺環境の中に、リンパ腫へと進展する発がん前駆体細胞が発生する。この前駆体細胞の特徴、関連する遺伝子を明らかにした。クローナル増殖が第一の特色であるが、分化能を保持したものと消失した細胞が存在し、分化停止にはBcl11bが関与する。興味深いことに、このBcl11bは腸管腫瘍発症の修飾遺伝子としても働く。さらに、発がん促進因子としてSirt4を候補遺伝子とした。

Research Products

• [Journal Article] An essential developmental checkpoint for production of the T cell lineage. (2010)
  • Author(s): Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano-Satoh A, Kominami R, Katsura Y, Kawamoto H
  • Journal Title: Science (in press)
  • Peer Reviewed
• [Journal Article] Bcl11b heterozygosity promotes clonal expansion and differentiation arrest of thymocytes inγ-irradiated mice. (2010)
  • Author(s): Go R, Hirose S, Morita S, Yamamoto T, Katsuragi Y, Mishima Y, Kominami R
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Clonally expanding thymocytes having lineage capability inγ-ray induced mouse atrophic thymus. (2010)
  • Author(s): Yamamoto T, Morita S, Go E, Obata M, Katsuragi Y, Fujita Y, Maeda Y, Yokoyama M, Aoyagi Y, Ichikawa H, Mishima Y, Kominami R
  • Journal Title: Int. J. Radiation Oncology Biol. 77 Pages: 235-243
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bcl11b and H2AX induced blast crisis of chronic myelogenous leukemia in a transgenic mouse model. (2009)
  • Author(s): Nagamachi A, Yamasaki N, Miyazaki K, Oda H, Miyazaki M, Honda Z, Kominami R, Inaba T, Honda H
  • Journal Title: Cancer Science 100 Pages: 219-1226
  • Peer Reviewed
• [Journal Article] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma. (2009)
  • Author(s): Akulevich N, Saenko V, Rogounovitch T, Drozd V, Lushnikov E, Ivanov V, Mitsutake N, _ Kominami R, Yamashita S
  • Journal Title: Endocnine-Related Cancer 16 Pages: 491-503
  • Peer Reviewed
• [Journal Article] Effect of Bcl11b genotypes and gamma-radiation on the development of mouse thymic lymphomas. (2008)
  • Author(s): Yoshikai Y, Sato T, Morita S, Kohara Y, Takagi R, Mishima Y, Kominami R
  • Journal Title: Biochem Biophys Res Commun. 373 Pages: 282-285
  • Peer Reviewed
• [Journal Article] Mtf-1lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice afterγ-irradiation. (2007)
  • Author(s): Maruyama M, Yamamoto T, Kohara Y, Katsuragi Y, Mishima Y, Aoyagi Y, Kominami R
  • Journal Title: Biochem. Biophys. Res. Commun. 354 Pages: 209-215
  • Peer Reviewed
• [Journal Article] Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development. (2007)
  • Author(s): Kamimura K, Ohi H, Kubota T, Okazuka K, Yoshikai Y, Wakabayashi Y, Aoyagi Y, Mishima Y, Kominami R
  • Journal Title: Biochem. Biophys. Res. Commun 355 Pages: 538-542
  • Peer Reviewed
• [Journal Article] Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times afterγ-irradiation. (2007)
  • Author(s): Ohi H, Mishima Y, Kamimura K, Maruyama M, Sasai K, Kominami R
  • Journal Title: Oncogene 26 Pages: 5280-5289
  • Peer Reviewed
• [Journal Article] Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress andd amages. (2007)
  • Author(s): Kamimura K, Mishima Y, Obata M, Endo T, Aoyagi Y, Kominami R
  • Journal Title: Oncogene 26 Pages: 5840-5850
  • Peer Reviewed
• [Journal Article] Trp53 affects the developmental anomaly of clefts of the palate in irradiated mouse embryos but not clefts of the lip with or without the palate. (2006)
  • Author(s): Narai S, Kodama Y, Maeda Y, Yokoyama M, Takagi R, Kominami R
  • Journal Title: Radiation Research 166 Pages: 877-882
  • Peer Reviewed
• [Journal Article] Expression of TCRαβpartly rescues developmental arrest and apoptosis ofαβT cells in Bcl11b-/-mice. (2006)
  • Author(s): Inoue J, Kanefuji T, Okazuka K, Watanabe H, Mishima Y, Kominami R
  • Journal Title: J. Immunology 176 Pages: 5871-5879
  • Peer Reviewed
• [Journal Article] Radiation carcinogenesis in mouse thymic lymphomas. (2006)
  • Author(s): Kominami R, Niwa O
  • Journal Title: Cancer Science 97 Pages: 575-581
  • Peer Reviewed
• [Presentation] Dose-dependent effect of zinc finger transcription factor Bcl111b on differentiation of cytotoxic T cells. (2008)
  • Author(s): Ryo Kominami, Satoshi Hirose, Ryota Ishizawa, Yoshinori Katsuragi, Yoshiya Sakuraba, Yoichi Gondo
  • Organizer: 22nd International Mammalian Genome Conference
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2008-11-05
• [Book] Radiation Health Risk Sciences (Eds, Nakashima, et al,)(Springer Library of Congress Control Number:2008937558, γ-Ray-Induced mouse Thymic Lymphomas:Bcl11b Inactivation and Prelymphoma cells) (2009)
  • Author(s): R Kominami, H Ohi, K Kamimura, M Maruyama, T Yamamoto, K Takaku, S Morita, R Go, Y Mishima
  • Total Pages: 232-239
  • Publisher: Springer