Isolation and characterization of cancer-related genes in mouse models

• Project/Area Number: 17013033
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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) ; HIROSE Satoshi 新潟大学, 医歯学系, 助教 (10415276) ; KATSURAGI Yoshinari 新潟大学, 医歯学系, 助教 (60401759) ; OBATA Miki 新潟大学, 医学部, 教務職員 (00420307) ; INOUE Jun 新潟大学, 医歯学系, 助手 (70323962)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥49,700,000 (Direct Cost: ¥49,700,000); Fiscal Year 2009: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2008: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2007: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2006: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: 研究分担者 / Bcl11b遺伝子 / がん抑制遺伝子 / 細胞増殖 / アポトーシス / 機能解析 / Bcl11b / Wnt/β-cateninシグナル / 大腸がん / TOP/FOPflash / 亜鉛フィンガードメイン / リンパ腫 / Bclllb遺伝子 / 胸腺リンパ腫 / Chk1

Research Abstract

Analysis of radiation-induced thymic lymphomas and atrophic thymuses revealed that Bcl11b functions as a suppressor at an early stage of the lymphoma development. Bcl11b transcription factor downregulates Chk1 check point kinase and its targets include cell cycle inhibitors such as p27 kip1 and p57 kip2 and also β-catenin. Deregulation of these proteins in Bcl11b heterozygous mice contributes to development of lymphomas and colon cancers.

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 329 Pages: 93-96
  • Peer Reviewed
• [Journal Article] Bclllb heterozygosity promotes clonal expansion and differentiation arrest of thymocytes in y-irradiated mice. (2010)
  • Author(s): Go R, Hirose S, Morita S, Yamamoto T, Katsuragi Y, Mishima Y, Kominami R.
  • Journal Title: Cancer Science 101 Pages: 347-1353
  • Peer Reviewed
• [Journal Article] Clonally expanding thymocytes having lineage capability in y-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] 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 T, Fujita Y, Maeda Y, Yokoyama M, Aoyagi Y, Ichikawa H, Mishima Y, Kominami R.
  • Journal Title: Int.J.Radiation Oncology Biol Phys Volume: 77 Pages: 235-243
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bclllb 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: 1219-1226
  • 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
  • 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, Ivanov VK, Mitsutake N, Kominami R.
  • Journal Title: Endocr Relat Cancer Volume: 16 Pages: 491-503
  • NAID: 120006984014
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bcl11b 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 Volume: 100 Pages: 1219-1226
  • NAID: 10027191952
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bel11b 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: Endocnine-Related Gancer 16(In press)
  • Peer Reviewed
• [Journal Article] Effect of Bclllb 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 Bel11b genotypes and gamma-radiation on the deve lopment 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 after γ-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 Bclllb 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 after y-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 Bclllb 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] Haploinsufficiency of Bcll1b for suppression of lymphomagenesis and thymocyte development. (2007)
  • Author(s): K. Kamimura
  • Journal Title: Biochemical and Biophysical Research Communications 355 Pages: 538-542
  • Peer Reviewed
• [Journal Article] Lack of Bcl11b 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 Bcl11b 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-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
• [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 of αβT cells in Bclllb-/-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] Radiation carcinogenesis in mouse thymic lymphomas. (2006)
  • Author(s): R.Kominami
  • Journal Title: Cancer Science 97 Pages: 575-581
  • NAID: 10018175404
• [Journal Article] Expression of TCRαβ partly rescues developmental arrest and apoptosis of αβT cells in Bcl11b-/- micel. (2006)
  • Author(s): J.Inoue
  • Journal Title: The Journal of Immunology 176 Pages: 5871-5879
• [Journal Article] Expression of TCRab partly rescues developmental arrest and apoptosis of ab T cells in Bcl11b^<-/->mice^1 (2006)
  • Author(s): Jun Inoue
  • Journal Title: The Journal of Immunology (発表予定)
• [Journal Article] Radiation carcinogenesis in mouse thymic lymphomas (2006)
  • Author(s): Ryo Kominami
  • Journal Title: Cancer Science (発表予定)
  • NAID: 10018175404
• [Journal Article] Mutant analysis reveals whirlin as a dynamic organizer in the growing hair cell stereocilium. (2005)
  • Author(s): Y.Kikkawa
  • Journal Title: Human Molecular Genetics 14(3) Pages: 391-400
• [Journal Article] Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas : role of Trp53 and radiation. (2005)
  • Author(s): T.Kubota
  • Journal Title: Radiation research 163(2) Pages: 159-164
• [Journal Article] Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. (2005)
  • Author(s): P.Arlotta
  • Journal Title: Neuron 45(2) Pages: 207-221
• [Presentation] Dose-dependent effect of zinc finger transcription factor Bcllllb 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, Prague
  • 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
• [Book] γ-Ray-Induced Mouse Thymic Lymphomas : Bclllb Inactivation and Prelymphoma Cells. Springer Library of Congress Control Number : 2008937558(Eds, Nakashima et al)(Radiation Health Risk Sciences) (2009)
  • Author(s): R Kominami, H Ohi, K Kamimura, M Maruyama, T Yamamoto, K Takaku, S Morita, R Go, Y Mishima.
• [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
• [Book] γ-Ray-Induced mouse Thymic Lymphomas : Bcl11b Inactivation and Prelymphoma cells. Radiation Health Risk Sciences 印刷中 (2009)
  • Author(s): R kominami
  • Publisher: Springer Library of Congress Control