Molecular mechanisms of development of stomach cancer by Epstein-Barr virus

• Project/Area Number: 17013002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hokkaido University
• Principal Investigator: TAKADA Kenzo Hokkaido University, 遺伝子病制御研究所, 教授 (30133721)
• Co-Investigator(Kenkyū-buntansha): MARUO Seiji 北海道大学, 遺伝子病制御研究所, 准教授 (70292018) ; IWAKIRI Dai 北海道大学, 遺伝子病制御研究所, 助教 (10307853)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥53,500,000 (Direct Cost: ¥53,500,000); Fiscal Year 2009: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2008: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2007: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2006: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2005: ¥10,700,000 (Direct Cost: ¥10,700,000)
• Keywords: 胃がん / ウイルス / RNA / サイトカイン / 自然免疫 / 分子機構 / EBウイルス / 溶解感染 / IL13 / Bリンパ球 / トランスフォーメーション / EBER / トランスジェニックマウス / 小RNA / BARF1 / RIG-I / TLR3 / IGF-1 / インターフェロン / 発がん

Research Abstract

In most people, Epstein-Barr virus (EBV) is maintained without specific manifestations, but is occasionally associated with various malignancies including lymphoma in immunodeficient hosts and gastric carcinoma. Previously, we have reported that EBV-encoded non-coding RNA (EBER) plays critical roles in oncogenesis. In this research, we have demonstrated that EBER exerts its oncogenic activity by utilizing an innate immunity system.

Research Products

• [Journal Article] Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Burkitt lymphoma. (2010)
  • Author(s): Watanabe, A., Maruo, S., Ito, T., Ito, M., Takada, K.
  • Journal Title: J. Virol. 84 Pages: 2893-2901
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Burkitt lymphoma (2010)
  • Author(s): Watanabe, A.
  • Journal Title: J.Virol. 84 Pages: 2893-2901
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival fact or in Burkitt lymphoma. (2010)
  • Author(s): Watanabe, A.
  • Journal Title: J.Virol. 84 Pages: 2893-2901
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3. (2009)
  • Author(s): Iwakiri, D., Zhou, L., Samanta, M., Matsumoto, M., Ebihara, T., Seya, T., Imai, S., Fujieda, M., Kawa, K., Takada, K.
  • Journal Title: J. Exp. Med. 206 Pages: 2091-2099
  • NAID: 120001629790
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation (2009)
  • Author(s): Katsumura, K.R.
  • Journal Title: J.Gen.Virol. 90 Pages: 2331-2341
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus(EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3 (2009)
  • Author(s): Iwakiri, D.
  • Journal Title: J.Exp.Med. 206 Pages: 2091-2099
  • NAID: 120001629790
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation. (2009)
  • Author(s): Katsumura, K.R.
  • Journal Title: J.Gen.Virol. 90 Pages: 2331-2341
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3. (2009)
  • Author(s): Iwakiri, D.
  • Journal Title: J.Exp.Med. 206 Pages: 2091-2099
  • NAID: 120001629790
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded small RNA (EBER) induces IL-10 through RIG-I-mediated IRF-3 signaling. (2008)
  • Author(s): Samanta, M., Iwakiri, D., Takada, K.
  • Journal Title: Oncogene 27 Pages: 4150-4160
  • Peer Reviewed
• [Journal Article] Reconstitution of nasopharyngeal carcinoma-type Epstein-Barr virus infection induces tumorigenicity. (2008)
  • Author(s): Seto, E., Ooka, T., Middeldorp, J., Takada, K.
  • Journal Title: Cancer Res. 68 Pages: 1030-1036
  • Peer Reviewed
• [Journal Article] Reconstitution of nasopharyngeal carcinoma-type Epstein-Barr virus infection induces tumorigenicity. (2008)
  • Author(s): Seto, E.
  • Journal Title: Cancer Res. 68 Pages: 1030-1036
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus (EBV)-encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-induced B-cell growth transformation (2007)
  • Author(s): Wu, Y., Maruo, S., Yajima, M., Kanda, T., Takada, K.
  • Journal Title: J. Virol. 81 Pages: 11236-11245
  • NAID: 120000955809
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus(EBV)-encoded RNA2(EBER2)but not EBER1 plays a critical role in EBV-induced B-cell growth transformation. (2007)
  • Author(s): Wu, Y
  • Journal Title: J. Virol. 81 Pages: 11236-11245
  • Peer Reviewed
• [Journal Article] EB virus-encoded RNAs (EBERs) are recognized by RIG-I and activate signaling to induce type I IFN. (2006)
  • Author(s): Samanta, M., Iwakiri, D., Kanda, T., Imaizumi, T., Takada, K.
  • Journal Title: EMBO J. 25 Pages: 4207-4214
  • Peer Reviewed
• [Journal Article] EB virus-encoded RNAs (EBERs) are recognized by RIG-I and activate signaling to induce type I IFN. (2006)
  • Author(s): Samanta, M.
  • Journal Title: EMBO J. 25 Pages: 4207-4214
• [Journal Article] Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells. (2006)
  • Author(s): Maruo, S.
  • Journal Title: Proc. Nat. Acad. Sci. USA 103 Pages: 19500-19505
  • NAID: 120000949900
• [Journal Article] Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate early gene following primary infection of B-lymphocytes. (2006)
  • Author(s): Wen, W.
  • Journal Title: J. Virol. 81 Pages: 1037-1042
• [Journal Article] Epstein-Barr virus (EBV) genome and expression in breast cancer tissue : effect of EBV infection on resistance to paclitaxel (Taxol). (2006)
  • Author(s): Arbach, H.
  • Journal Title: J. Virol. 80 Pages: 845-853
• [Journal Article] Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. (2006)
  • Author(s): Kim, D. N.
  • Journal Title: J. Virol. 81 Pages: 1033-1036
• [Journal Article] Epstein-Barr virus (EBV) genome and expression in breast cancer tissue : effect of EBV infection on resistance to paclitaxel (Taxol). (2006)
  • Author(s): Arbach, H.
  • Journal Title: J.Virol. 80 Pages: 845-853
• [Journal Article] Epstein-Barr virus-encoded poly(A)- RNA confers resistance to apoptosis mediated through Fas by blocking the PKR pathway in human epithelial Intestine 407 cells. (2005)
  • Author(s): Nanbo, A., Takada, K.
  • Journal Title: J. Virol. 79 Pages: 12280-12285
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression: implication of a new EBV latency type. (2005)
  • Author(s): Seto, E., Yang, L., Middeldorp, J., Sheen, J.S., Chen, J.Y., Eizuru, Y., Takada, K.
  • Journal Title: J. Med. Virol. 76 Pages: 82-88
  • Peer Reviewed
• [Journal Article] Role of Epstein-Barr virus (EBV)-encoded RNA (EBER) for efficient EBV-induced B-lymphocyte growth transformation. (2005)
  • Author(s): Yajima, M., Kanda, T., Takada, K.
  • Journal Title: J. Virol. 79 Pages: 4298-4307
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma cell lines. (2005)
  • Author(s): Iwakiri, D., Sheen, T. -S., Chen, J. -Y., Huang, D.P., Takada, K.
  • Journal Title: Oncogene 24 Pages: 1767-1773
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma cell lines. (2005)
  • Author(s): Iwakiri, D.
  • Journal Title: Oncogene 24 Pages: 1767-1773
• [Journal Article] Role of Epstein-Barr virus (EBV)-encoded RNA (EBER) for efficient EBV-induced B-lymphocyte growth transformation. (2005)
  • Author(s): Yajima, M.
  • Journal Title: J.Virol. 79 Pages: 4298-4307
• [Journal Article] Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression : implication of a new EBV latency type. (2005)
  • Author(s): Seto, E.
  • Journal Title: J.Med.Virol. 76 Pages: 82-88
• [Journal Article] Epstein-Barr virus-encoded poly(A)-RNA confers resistance to apoptosis mediated through Fas by blocking the PKR pathway in human epithelial Intestine 407 cells. (2005)
  • Author(s): Nanbo, A.
  • Journal Title: J.Virol. 79 Pages: 12280-12285
• [Journal Article] Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress. (2005)
  • Author(s): Wong, H.L.
  • Journal Title: Mol.Carcinogenesis 44 Pages: 92-101
• [Journal Article] Epstein-Barr virus-encoded small RNA(EBER)induces IL-10 through RIG-I-mediated IRF-3 signaling.
  • Author(s): Samanta, M.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Symmetrical localization of extrachromosomally-replicating viral episomes on sister chromatids.
  • Author(s): Kanda, T.
  • Journal Title: J. Cell Sci. (in press)
• [Presentation] Epstein-Barr virus-induced oncogenesis through utilizing the innate immunity system. (2008)
  • Author(s): Takada, K., Iwakiri, D., M. Samanta
  • Organizer: 13th Biennial Conference of the International Association for Research on Epstein-Barr Virus and Associated Diseases
  • Place of Presentation: Guangzhou
• [Presentation] EBVによる自然免疫系の修飾と発がん (2008)
  • Author(s): 高田賢蔵、岩切大
  • Organizer: 第67回日本癌学会学術総会「ウイルス発がん」
  • Place of Presentation: 名古屋
• [Presentation] EBV-encoded non-coding RNA exerts oncogenic activity by utilizing the innate immunity system. (2007)
  • Author(s): Takada, K
  • Organizer: 13rd International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections
  • Place of Presentation: Palazzo del Popolo Orvieto, Italy
  • Year and Date: 2007-11-06
• [Presentation] Role of Epstein-Barr virus-encoded non-coding RNAs and innate immunity in oncogenesis. (2007)
  • Author(s): Takada, K., Iwakiri, D.
  • Organizer: 第66回日本癌学会学術総会シンポジウム「ウイルス発がん」
  • Place of Presentation: 横浜
• [Presentation] EBウイルスと癌 (2007)
  • Author(s): 高田賢蔵
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪
• [Presentation] Epstein-Barr virus and gastric carcinoma: role of virus-encoded small RNAs and innate immunity in oncogenesis. (2007)
  • Author(s): Takada, K.
  • Organizer: The Croucher Foundation Advanced Study Institute: Viruses and cancer
  • Place of Presentation: Hong Kong
• [Presentation] EBウイルスと発癌 (2006)
  • Author(s): 高田賢蔵
  • Organizer: 第54回日本ウイルス学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] EBV-encoded non-coding RNAs and oncogenesis. (2006)
  • Author(s): Takada, K.
  • Organizer: The 19th International Symposium of Foundation for Promotion of Cancer Research.[Infection, Cancer and Prevention]
  • Place of Presentation: Tokyo
• [Presentation] EBV: establishment of latent infection and reactivation. (2006)
  • Author(s): Takada, K.
  • Organizer: The 19th International Symposium of Foundation for Promotion of Cancer Research.[Infection, Cancer and Prevention]
  • Place of Presentation: Tokyo
• [Book] Epstein-Barr Virus(Epstein-Barr virus and gastric cancers. ed. Robertson, E.S.) (2005)
  • Author(s): Iwakiri, D., Takada, K.
  • Publisher: Caister Academic Press, Norfolk, UK
• [Book] Epstein-Barr Virus (Role of EBERs. ed. Robertson, E.S.) (2005)
  • Author(s): Takada, K.
  • Publisher: Caister Academic Press, Norfolk, UK