Research on the molecular mechanism of carcinogenesis using retroviral insertional mutagenesis

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013086
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: NAKAMURA Takuro Japanese Foundation For Cancer Research, 癌研究所 発がん研究部, 部長 (00180373)
• Co-Investigator(Kenkyū-buntansha): TURUYAMA Tatuaki 京都大学, 医学研究科 病理系法医学教室, 講師 (00303842) ; TANAKA Miwa 財団法人 癌研究会, 癌研究所発がん研究部, 研究員 (70345883)
• Project Period (FY): 2005 – 2009
• Keywords: レトロウィルス挿入変異 / 協調遺伝子 / 骨髄性白血病 / 間葉系腫瘍 / ホメオボックス遺伝子 / 前駆細胞 / トランスポゾン / Trib1

Research Abstract

To clarify the molecular mechanism of carcinogenesis, a series of disease genes that are important for cancer progression by using retrovirus insertional mutagenesis. Trib1 has been identified as a specific cooperative gene for Hoxa9/Meis1, and its modulation effects for MEK and C/Ebpa is required for leukemogenesis. Seven common integration sites have been identified as candidate cooperative genes for the mutation of Bash that is a preB-ALL tumor suppressor. Application of the mutagenesis system on non-hematopoietic neoplasms by utilizing the in vitro system of colon epithelial cells and the Piggybac transposon.

Research Products

• [Journal Article] Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance (2010)
  • Author(s): Fujino T, Nomura K, Ishikawa Y, Makino H, Umezawa A, Aburatani H, Nagasaki K, Nakamura T.
  • Journal Title: Am J Pathol 176 Pages: 1973-1982
  • Peer Reviewed
• [Journal Article] A quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability (2010)
  • Author(s): Kaszynski RH, Akatsuka S, Hiratsuka T, Jin G, Ozeki M, Okuno T, Nakamura T, Manabe T, Takakuwa T, Hiai H, Toyokuni S, Tamaki K, Tsuruyama T.
  • Journal Title: Cancer Sci 101 Pages: 800-805
  • Peer Reviewed
• [Journal Article] Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS (2009)
  • Author(s): Makino H, Toyoda M, Matsumoto K, Saito H, Nishino K, Fukawatase Y, Machida M, Akutsu H, Uyama T, Miyagawa Y, Okita H, Kiyokawa N, Fujino T, Ishikawa Y, Nakamura T, Umezawa A.
  • Journal Title: Exp Cell Res 315 Pages: 2727-2740
  • Peer Reviewed
• [Journal Article] Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia (2009)
  • Author(s): Miyazaki K, Yamasaki N, Oda H, Kuwata T, Kanno Y, Miyazaki M, Komeno Y, Kitaura J, Honda Z, Warming S, Jenkins NA, Copel, NG, Kitamura T, Nakamura T, Honda H.
  • Journal Title: Blood 113 Pages: 4702-4710
  • Peer Reviewed
• [Journal Article] Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry (2009)
  • Author(s): Komai Y, Fujiwara M, Fujii Y, Mukai H, Yonese J, Kawakami S, YamamotoH, Migita T, Ishikawa Y, Kurata M, Nakamura T, Fukui I.
  • Journal Title: Clin Cancer Res 15 Pages: 1170-1176
  • Peer Reviewed
• [Journal Article] A DNA transposon based approach to validate oncogenic mutations in the mouse (2008)
  • Author(s): Su Q, Prosser HM, Campos LS, Ortiz M, Nakamura T, Warren M, Dupuy AJ, Jenkins NA, Copel, NG, Bradley A, Liu P.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 19904-19909
  • Peer Reviewed
• [Journal Article] BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body (2008)
  • Author(s): Kuwata T, Nakamura T.
  • Journal Title: Genes Cells 13 Pages: 931-940
  • Peer Reviewed
• [Journal Article] Bone marrow pre-B expansion by SL/Kh Bomb1 locus: not sufficient for lymphomagenesis (2008)
  • Author(s): Hiratsuka T, Tsuruyama T, Kaszynski R, Kometani K, Minato N, Nakamura T, Tamaki K, Hiai H.
  • Journal Title: Leukemia Res 32 Pages: 309-314
  • Peer Reviewed
• [Journal Article] Identification of candidate cooperative genes of the Apc mutation in transformation of the colon epithelial cell by retroviral insertional mutagenesis (2008)
  • Author(s): Tanaka M, Jin G, Yamazaki Y, Takahara T, Takuwa M, Nakamura T.
  • Journal Title: Cancer Sci 99 Pages: 979-985
  • Peer Reviewed
• [Journal Article] Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis (2007)
  • Author(s): Jin G, Yamazaki Y, Takuwa M, Takahara T, Kaneko K, Kuwata T, Miyata S, Nakamura T.
  • Journal Title: Blood 109 Pages: 3998-4005
  • Peer Reviewed
• [Journal Article] Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation (2006)
  • Author(s): Kawamura-Saito M, Yamazaki Y, Kaneko K, Kawaguchi N, Kanda H, Mukai H, Gotoh T, Motoi T, Fukayama M, Aburatani H, Takizawa T, Nakamura T.
  • Journal Title: Hum Mol Genet 15 Pages: 2125-213
  • Peer Reviewed
• [Journal Article] Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice (2005)
  • Author(s): Yamashita N, Osato M, Huang L, Yanagida M, Kogan SC, Iwasaki M, Nakamura T, Shigesada K, Asou N, Ito Y.
  • Journal Title: Br J Haematol 131 Pages: 495-507
  • Peer Reviewed
• [Journal Article] Increased dose of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice (2005)
  • Author(s): Yanagida M, Osato M, Yamashita N, Liqun H, Jacob B, Wu F, Cao X, Nakamura T, Yokomizo T, Takahashi S, Yamamoto M, Shigesada K, Ito Y.
  • Journal Title: Oncogene 24 Pages: 4477-4485
  • Peer Reviewed
• [Journal Article] NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain proteins (2005)
  • Author(s): Nakamura T.
  • Journal Title: Int J Hematol 82 Pages: 21-27
  • Peer Reviewed
• [Journal Article] Meis and Hox: a mighty pair defeats apoptosis (2005)
  • Author(s): Nakamura T.
  • Journal Title: Blood 105 Pages: 909-910
  • Peer Reviewed
• [Journal Article] Retroviral insertional mutagenesis identifies oncogene cooperation (2005)
  • Author(s): Nakamura T.
  • Journal Title: Cancer Sci 96 Pages: 7-12
  • Peer Reviewed
• [Journal Article] EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12) (2005)
  • Author(s): Yamaguchi S, Yamazaki Y, Ishikawa Y, Kawaguchi N, Mukai H, Nakamura T.
  • Journal Title: Genes Chromosomes Cancer 43 Pages: 217-222
  • Peer Reviewed
• [Journal Article] Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model (2005)
  • Author(s): Iwasaki M, Kuwata T, Yamazaki Y, Jenkins NA, Copel, NG, Osato M, Ito Y, Kroon E, Sauvageau G, Nakamura T.
  • Journal Title: Blood 105 Pages: 784-793
  • Peer Reviewed
• [Journal Article] Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in IL-7 signaling pathway in B lymphoblastic lymphomas
  • Author(s): Tsuruyama T, Imai Y, Takeuchi H, Hiratsuka T, Maruyama Y, Kanaya K, Kaszynski R, Jin G, Okuno T, Ozeki M, Nakamura T, Takakuwa T, Manabe T, Tamaki K, Hiai H.
  • Journal Title: J Leukocyte Biol (in press)
  • Peer Reviewed
• [Presentation] Molecular dissection of myeloid leukemogenesis (2009)
  • Author(s): 中村卓郎
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] The role of homedomain proteins in myeloid leukemogenesis (2009)
  • Author(s): Nakamura T
  • Organizer: US-Japan Cooperative Cancer Workshop on Stem Cells in Normal and Malignant Hematopoiesis
  • Place of Presentation: ハワイ
  • Year and Date: 2009-03-29
• [Presentation] The role of homeodomain genes in myeloid leukemogenesis (2009)
  • Author(s): Nakamura T
  • Organizer: International Symposium on New Frontiers in Cancer Research
  • Place of Presentation: 札幌
  • Year and Date: 2009-03-18
• [Presentation] ホメオドメイン遺伝子経路を巡る白血病発症機構 (2009)
  • Author(s): 中村卓郎
  • Organizer: 平成20年度がん特定研究5領域合同シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-02-03
• [Presentation] Identification of new molecular pathways in carcinogenesis by retroviral tagging (2008)
  • Author(s): Nakamura T
  • Organizer: 金沢大学がん生物国際シンポジウム2008
  • Place of Presentation: 金沢
  • Year and Date: 2008-01-24
• [Presentation] Understanding multi-step carcinogenesis using retroviral insertional mutagenesis (2007)
  • Author(s): Nakamura T
  • Organizer: The 12th Korea-Japan Cancer Research Workshop
  • Place of Presentation: 札幌
  • Year and Date: 2007-12-22
• [Presentation] Molecular mechanisms of Hoxa9/Meis1-induced myeloid leukemogenesis (2007)
  • Author(s): Nakamura T
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Molecular mechanisms of Hoxa9/Meis1-induced myeloid leukemogenesis (2007)
  • Author(s): Nakamura T
  • Organizer: 7th International Workshop on Molecular Aspects of Myeloid Stem Cell Development and Leukemia
  • Place of Presentation: Annapolis, MD, USA
  • Year and Date: 2007-05-15
• [Presentation] Homeodomain proteins in leukemogenesis and hematopoiesis (2007)
  • Author(s): Nakamura T
  • Organizer: USA-Japan Cooperative Seminar on Hematological Malignancy
  • Place of Presentation: Kauai, HI, USA
  • Year and Date: 2007-03-21
• [Presentation] レトロウィルス挿入変異を用いた白血病発症機構の解析 (2006)
  • Author(s): 中村卓郎
  • Organizer: 第23回日本疾患モデル学会総会シンポジウム
  • Place of Presentation: 伊香保
  • Year and Date: 2006-11-30
• [Presentation] レトロウィルス挿入変異を用いた白血病発症過程の解析 (2006)
  • Author(s): 中村卓郎
  • Organizer: 第65回日本癌学会総会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-28
• [Presentation] Molecular evolution of Hoxa9/Meis1-induced myeloid leukemia (2006)
  • Author(s): Nakamura T
  • Organizer: International Symposium on Functional Mouse Genomics
  • Place of Presentation: Frederick, MD, USA
  • Year and Date: 2006-07-21
• [Presentation] Hoxa9/Meis1 cooperation and the molecular pathway in leukemogenesis (2006)
  • Author(s): Nakamura T
  • Organizer: EMBO/SEMM Workshop on homeodomain proteins, hematopoietic development and leukemias
  • Place of Presentation: Riva del Garda, Italy
  • Year and Date: 2006-03-25
• [Presentation] レトロウィルス挿入変異システムを用いた発がん分子過程の解析 (2006)
  • Author(s): 中村卓郎
  • Organizer: 第3回日本癌学会カンファレンス
  • Place of Presentation: 蓼科
  • Year and Date: 2006-03-10
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/tci/carcinogenesis/index.html