Host factors and genetic mutations in radiation carcinogenesis

• 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
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥52,130,000 (Direct Cost: ¥40,100,000、Indirect Cost: ¥12,030,000); Fiscal Year 2009: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2008: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2007: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2006: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
• 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 / 放射線ターゲット細胞 / 放射線発がん初期過程 / Bcl11b / 癌細胞幹細胞 / 腸管腫瘍 / β-カテニン / がん抑制遺伝子 / 細胞増殖 / アポトーシス / リンパ腫 / Bclllb遺伝子 / がん / 電離放射線 / 遺伝学 / シグナル伝達

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] Transient exposure of neonatal mice to neuregulin-1 results in hyperd opaminergic states in adulthood : implication in neurodevelopmental hypothesis for schizophrenia. (2010)
  • Author(s): Kato T, Sotoyama H, Kakita A, Kominami R, Hirokawa S, Ozaki M, Takahashi H, Nawa H.
  • Journal Title: Mol Psychiatry (In Press)
  • Peer Reviewed
• [Journal Article] Clonally expanding thymocytes having lineage capability in γ-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 Phys 77(1) Pages: 235-243
  • Peer Reviewed
• [Journal Article] Bclllb heterozygosity promotes clonal expansion and differentiation arrest of thymocytes in γ-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] 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
  • NAID: 10027191952
  • 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
  • NAID: 120006984014
  • Peer Reviewed
• [Journal Article] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma. (2009)
  • Author(s): Akulevich NM, Saenko VA, Rogounovitch TI, Drozd VM, Lushnikov EF, IvanovVK, Mitsutake N, Kominami R.
  • Journal Title: Endocr Relat Cancer 16 Pages: 491-503
  • NAID: 120006984014
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bclllb and H2AX induces 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: 1219-1226
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Ryo kominami
  • Journal Title: γ-Ray-Induced mouse Thymic Lymphomas : Radiation Health Risk Sciences(Bclllb Inactivation and Prelymphoma cells.)(Springer Library of Congress Control) Pages: 232-239
• [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): A. Nagamachi
  • Journal Title: Cancer Science (In press)
  • Peer Reviewed
• [Journal Article] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma. (2009)
  • Author(s): M. Natallia
  • Journal Title: Endocrine-Related Cancer 16(In press)
  • 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] Effect of Bcl11b genotypes and gamma-radiation on the development of mouse thymic lymphomas. (2008)
  • Author(s): Y. Yoshikai
  • 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] Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation (2007)
  • Author(s): H. Ohi, Y. Mishima, K. Kamimura, M. Maruyama, K. Sasai and R. Kominami
  • Journal Title: Oncogene 26 Pages: 5280-5289
• [Journal Article] Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after γ-irradiation. (2007)
  • Author(s): M. Maruyama
  • Journal Title: Biochemical and Biophysical Research Communications 354 Pages: 209-215
  • Peer Reviewed
• [Journal Article] Lack of Bcll1b tumor suppressor results in vulnerability to DNA replication stress and damages. (2007)
  • Author(s): K. Kamimura
  • Journal Title: Oncogene 26 Pages: 5840-5850
  • Peer Reviewed
• [Journal Article] Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation. (2007)
  • Author(s): H. Ohi
  • Journal Title: Oncogene 26 Pages: 5280-5289
  • Peer Reviewed
• [Journal Article] Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development. (2007)
  • Author(s): K.Kamimura
  • Journal Title: Biochemical and Biophysical Research Communications 355 Pages: 538-542
• [Journal Article] Lack of Bcl1 1b tumor suppressor results in vulnerability to DNA replication stress andd amages. (2007)
  • Author(s): K.Kamimura
  • Journal Title: Oncogene (印刷中)
• [Journal Article] Multi-step lymphomagenesis deduced from DNA changes in thymic lymphomas and atrophic thymuses at various times after γ-irradiation. (2007)
  • Author(s): H.Ohi
  • Journal Title: Oncogene (印刷中)
• [Journal Article] Mtf-l lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after γ-irradiation. (2007)
  • Author(s): M.Maruyama
  • Journal Title: Biochemical and Biophysical Research Communications 354 Pages: 209-215
• [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
  • NAID: 10018175404
  • Peer Reviewed
• [Journal Article] Expression of TCRαβ partly rescues developmental arrest and apoptosis of αβT cells in Bcl1 1b-/- micel. (2006)
  • Author(s): J.Inoue
  • Journal Title: The Joumal of Immunology 176 Pages: 5871-5879
• [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): S.Narai
  • Journal Title: Radiation Research 166 Pages: 877-882
• [Journal Article] Predisposition to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1) (2005)
  • Author(s): Y. Tamura, M. Maruyama, Y. Mishima, H. Fujisawa, M. Obala, Y Kodauia, Y. Yoshikai, Y. Aoyagi, O. Niwa, W. Schaffner and R. Kominami
  • Journal Title: Oncogene 24 Pages: 399-406
• [Journal Article] Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas : role of Trp53 and radiation (2005)
  • Author(s): T. Kubota, Y. Yoshikai, Y Tamura, Y. Mishima, Y. Aoyagi, O. Niwa and R. Kominami
  • Journal Title: Radiation Research 163 Pages: 159-164
• [Presentation] γ線照射によるマウス萎縮胸腺内の前リンパ腫細胞形成には細胞増殖と分化停止が必要である (2009)
  • Author(s): 葛城美徳、郷梨江香、森田慎一、小幡美貴、木南凌
  • Organizer: 第52回日本放射線影響学会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-11
• [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
• [Presentation] Dose-dependent effect of Zinc-finger transcription factor Bcl11b on differentiation of cytotoxic cells (2008)
  • Author(s): Ryo kominami
  • Organizer: 22^<nd> International Mammalian Genome Conference
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2008-11-05
• [Presentation] Cellular and molecular characterization of pre-lymphoma cells developing in the strophic thymus of γ-irradiated mice (2008)
  • Author(s): Ryo kominami
  • Organizer: 第7回放射線生物学に関する日仏ワークショップ
  • Place of Presentation: 千葉市
  • Year and Date: 2008-10-14
• [Presentation] Dose-dependent effect of zinc fmger transcription factor Bc1111b on differentiation of cytotoxic T cells (2008)
  • Author(s): Ryo Kominami, Satoshi Hirose, Ryota Ishizawa, Yoshinori Katsuragi, Yoshiya Sakuraba, Yoichi Gondo
  • Organizer: 22^nd International Mammalian Genome Conference
  • Place of Presentation: Prague, Czech Republic
• [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
  • Publisher: Springer
• [Book] Radiation Health Risk Sciences(Nakashima, et.al(Eds))(γ-Ray-Induced mouse Thymic Lymphomas : Bc111b 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
  • Publisher: Springer
• [Book] γ-Ray-Induced mouse Thymic Lymphomas : Bcl11b Inactivation and Prelymphoma cells. Radiation Health Risk Sciences (2009)
  • Author(s): R kominami
  • Publisher: Springer Library of Congress Control(印刷中)