Carcinogenesis by a genome mutator AID

• Project/Area Number: 17013042
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Research Institute, Shiga Medical Center
• Principal Investigator: KINOSHITA Kazuo Research Institute, Shiga Medical Center, 遺伝子研究部門, 専門研究員 (50293874)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥48,500,000 (Direct Cost: ¥48,500,000); Fiscal Year 2009: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2008: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2007: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000); Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: AID / 発がん / 感染 / 慢性炎症 / 突然変異 / 肝臓がん / 皮膚がん / 体細胞突然変異 / クラススイッチ組換え / Creリコンビナーゼ

Research Abstract

免疫に関わる抗体の遺伝子に変異を入れて多様な抗体を作る酵素AIDが偶発的に抗体以外の遺伝子に変異を導入することにより発がんに至るという仮説を支持する以下の結果が得られた。(1) 肝炎ウイルスによる肝がんやピロリ菌による胃がんにAIDが存在している、(2) 肝臓でAIDが作られるマウスを遺伝子工学により作製すると肝臓がんが発症した。(3) AIDのないマウスでは実験的皮膚がんが起こりにくかった。

Research Products

• [Journal Article] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. (2009)
  • Author(s): Takai, A, Toyoshima, T, Uemura, M, Kitawaki, Y, Marusawa, H, Hiai, H, Yamada, S, Okazaki, IM, Honjo, T, Chiba, T, Kinoshita, K.
  • Journal Title: Oncogene 28 Pages: 469-478
  • Peer Reviewed
• [Journal Article] Carboxy-terminal domain of AID required for its mRNA complex formation in vivo. (2009)
  • Author(s): Nonaka, T, Doi, T, Toyoshima, T, Muramatsu, M, Honjo, T, Kinoshita, K.
  • Journal Title: Proc Natl Acad Sci U S A 106 Pages: 2747-51
  • Peer Reviewed
• [Journal Article] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations (2009)
  • Author(s): Takai, A., et al.
  • Journal Title: Oncogene 28 Pages: 469-478
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. (2008)
  • Author(s): Komori, J, Marusawa, H, Machimoto, T, Endo, Y, Kinoshita, K, Kou, T, Haga, H, Ikai, I, Uemoto, S, Chiba, T.
  • Journal Title: Hepatology 47 Pages: 888-896
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. (2008)
  • Author(s): Endo, Y, Marusawa, H, Kou, T, Nakase, H, Fujii, S, Fujimori, T, Kinoshita, K, Honjo, T, Chiba, T.
  • Journal Title: Gastroenterology 135
  • Peer Reviewed
• [Journal Article] Activation-induced, cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers (2008)
  • Author(s): Endo, Y., et al.
  • Journal Title: Gastroenterology 135 Pages: 889-898
  • Peer Reviewed
• [Journal Article] Carboxy-terminal domain of AID required for its mRNA complex formation in vivo (2008)
  • Author(s): Nonaka, T., et al.
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 2747-2751
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma (2008)
  • Author(s): Komori, J., et. al.
  • Journal Title: Hepatology 47 Pages: 888-896
  • Peer Reviewed
• [Journal Article] Helicobacter pylori infection triggers aberrant expression of activation- induced cytidine deaminase in gastric epithelium. (2007)
  • Author(s): Matsumoto, Y, Marusawa, H, Kinoshita, K, Endo, Y, Kou, T, Morisawa, T, Azuma, T, Okazaki, IM, Honjo, T, Chiba, T.
  • Journal Title: Nat Med 13 Pages: 470-6
  • Peer Reviewed
• [Journal Article] Ectopic expression of activation- induced cytidine deaminase in ulcerative colitis-associated colorectal cancers. (2007)
  • Author(s): Kou, T, Marusawa, H, Endo, Y, Nakase, H, Fujii, S, Kinoshita, K, Fujimori, T, Honjo, T, Chiba, T.
  • Journal Title: Gastroenterology 132
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice. (2007)
  • Author(s): Kotani, A, Kakazu, N, Tsuruyama, T, Okazaki, IM, Muramatsu, M, Kinoshita, K, Nagaoka, H, Yabe, D, Honjo, T.
  • Journal Title: Proc Natl Acad Sci U S A 104 Pages: 1616-20
  • Peer Reviewed
• [Journal Article] High expression of activation induced cytidine deaminase in human bile duct epithelium during cholangiocarcinogenesis. (2007)
  • Author(s): Komori, J, Marusawa, H, Machimoto, T, Endo, Y, Kinoshita, K, Kou, T, Haga, H, Ikai, I, Uemoto, S, Honjo, T, Chiba, T.
  • Journal Title: Gastroenterology 132
  • Peer Reviewed
• [Journal Article] Expression of activation-induced cytidine deaminase in human hepatocytes via NF-kappaB signaling. (2007)
  • Author(s): Endo, Y, Marusawa, H, Kinoshita, K, Morisawa, T, Sakurai, T, Okazaki, IM, Watashi, K, Shimotohno, K, Honjo, T, Chiba, T.
  • Journal Title: Oncogene 26 Pages: 5587-95
  • Peer Reviewed
• [Journal Article] Helicobacter pylorl infaction triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium (2007)
  • Author(s): Matsumoto, Y, et. al.
  • Journal Title: Nat Med 13 Pages: 470-476
  • Peer Reviewed
• [Journal Article] Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis (2007)
  • Author(s): Kou, T.et al.
  • Journal Title: Int. J. Cancer 120・3 Pages: 469-476
• [Journal Article] Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice (2007)
  • Author(s): Kotani, A. et al.
  • Journal Title: Proc. Natl. Acad. Sci. U S A 104・5 Pages: 1616-1620
• [Journal Article] Negative regulation of activation- induced cytidine deaminase in B cells. (2006)
  • Author(s): Muto, T, Okazaki, IM, Yamada, S, Tanaka, Y, Kinoshita, K, Muramatsu, M, Nagaoka, H, Honjo, T.
  • Journal Title: Proc Natl Acad Sci U S A 103 Pages: 2752-2757
  • Peer Reviewed
• [Journal Article] Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis. (2006)
  • Author(s): Kou, T, Marusawa, H, Kinoshita, K, Endo, Y, Okazaki, IM, Ueda, Y, Kodama, Y, Haga, H, Ikai, I, Chiba, T.
  • Journal Title: Int J Cancer 120 Pages: 469-76
  • Peer Reviewed
• [Journal Article] The dark side of activation-induced cytidine deaminase: relationship with leukemia and beyond. (2006)
  • Author(s): Kinoshita, K, Nonaka, T.
  • Journal Title: Int J Hematol 83 Pages: 201-7
  • NAID: 10017421763
  • Peer Reviewed
• [Journal Article] The dark side of activation-induced cytidine deaminase : relationship with leukemia and beyond (2006)
  • Author(s): Kinoshita, K. et al.
  • Journal Title: Int. J. Hematol. 83・3 Pages: 201-207
  • NAID: 10017421763
• [Journal Article] Identification of a specific domain required for dimerization of activation-induced cytidine deaminase (2006)
  • Author(s): Wang, J. et al.
  • Journal Title: J. Biol. Chem. 281・28 Pages: 19115-19123
• [Journal Article] Negative regulation of activation-induced cytidine deaminase in B cells (2006)
  • Author(s): Muto, T.et al.
  • Journal Title: Proc Natl Acad Sci U S A 103・8 Pages: 2752-2757
• [Journal Article] Role of DNA polymerase theta in tolerance of endogenous and exogenous DNA damage in mouse B cells (2006)
  • Author(s): Ukai, A.et al.
  • Journal Title: Genes Cells 11・2 Pages: 111-121
• [Journal Article] Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID (2006)
  • Author(s): Wakae, K.et al.
  • Journal Title: Int Immunol 18・1 Pages: 41-47
• [Presentation] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. (2009)
  • Author(s): Takai A, Toyoshima T, Uemura M, Niwa Y, Marusawa H, Hiai H, Honjo T, Chiba T, Kinoshita K
  • Organizer: 21st IUBMB and 12th EAOBMB International Congress of Biochemistry and Molecular Biology.
  • Place of Presentation: 上海(中国)
  • Year and Date: 2009-08-06
• [Presentation] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. (2009)
  • Author(s): Takai A, Toyoshima T, Uemura M, Niwa Y, Marusawa H, Hiai H, Honjo T, Chiba T, Kinoshita K.
  • Organizer: 21st IUBMB and 12th FAOBMB International Congress of Biochemistry and Molecular Biology.
  • Place of Presentation: 上海, 中国
• [Presentation] 発癌過程における遺伝子異常生成へのActivation-induced cytidine deaminase (AID)の関与 (2008)
  • Author(s): 遠藤容子, 他
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Activation-induced cytidine deaminase serves as a link between inflammation to colitis-associated colorectal cancers (2008)
  • Author(s): Endo Y., et al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] A novel mouse model of hepatocarcinogenesis triggered by activation-induced cytidine deaminase (AID) (2008)
  • Author(s): Takai A., et al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] A new mouse model of hepatocarcinogenesis triggered by activation-induced cytidine deaminase expressed in hepatic stem cells. (2008)
  • Author(s): Takai A, Marusawa H, Tabuchi Y, Ohtsuru S, Endo Y, Chiba T, Kinoshita K.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-04-12
• [Presentation] 発癌過程における遺伝子異常生成へのActivation-induced cytidine deaminase (AID)の関与 (2008)
  • Author(s): 遠藤容子、丸澤宏之、木下和生、本庶佑、千葉勉
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合 同大会
  • Place of Presentation: 神戸
• [Presentation] Activation- induced cytidine deaminase serves as a link between inflammation to colitis- associated colorectal cancers. (2008)
  • Author(s): Endo Y, Marusawa H, Kinoshita K, Kou T, Fujii S, Fujimori T, Chiba T.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 内在性変異原AIDによる抗体とがん細胞の進化 (2008)
  • Author(s): 木下和生
  • Organizer: 第80回日本遺伝学会大会
  • Place of Presentation: 名古屋
• [Presentation] Activation-induced cytidine deaminase links liver inflammation huznan hepatocarcinogenesis (2007)
  • Author(s): Endo, Y, et. al.
  • Organizer: Keystone Symposia: Frontiers in gastrointestinal cancer: molecular genetics inflammation, early detction and therapy
  • Place of Presentation: 北京(中国)
  • Year and Date: 2007-10-15
• [Presentation] Hepatitis C vixus triggers aberrant expression of actovaton-induced cytidine deaminase (AID) in human hepatocytss (2007)
  • Author(s): 遠藤 容子, 他
  • 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] 突然変異誘導因子AIDによる発がん (2005)
  • Author(s): 木下和生, 野中太一郎
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Remarks]
  • URL: http://homepage.mac.com/kkinoshi/lab/
• [Remarks]
  • URL: http://homepage.mac.com/kkinoshi/lab/
• [Remarks]
  • URL: http://homepage.mac.com/kkinoshi/lab/
• [Remarks]
  • URL: http://homepage.mac.com/kkinoshi/lab/