Analysis of synovial sarcoma oncogene SYT-SSX for development of new therapy

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390386
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: TANAKA Shinya Hokkaido University, 大学院・医学研究科, 教授 (70261287)
• Co-Investigator(Kenkyū-buntansha): NISHIHARA Hiroshi 北海道大学, 大学院・医学研究科, 准教授 (50322805) ; MINAMI Akio 北海道大学, 大学院・医学研究科, 教授 (20133738)
• Project Period (FY): 2007 – 2009
• Keywords: 滑膜肉腫 / SYT-SSX / トランスジェニックマウス / ノックアウトマウス / シグナル伝達 / CRK

Research Abstract

The purpose of this study is to analyze the transforming mechanism of human synovial sarcoma-associated oncogene SYT-SSX and to establish the basic system for the development of new therapy. We originally proved that SYT-SSX is responsible oncogene for human synovial sarcoma, and in this study, we found that signalling adaptor protein Crk is involved in malignant feature of synovial sarcoma and one of the map kinase family protein as p38 plays an important role. Furthermore, SYT-SSX transgenic mice which develop synovial sarcoma and also SYT knockout mice were established in this study. The mice model of human synovial sarcoma should be expected to provide versatile effect for the evaluation of new therapeutic reagents.

Research Products

• [Journal Article] Lab. Invest (2009)
  • Author(s): Kimura, T., Sakai, M., Tabu, K., Wang. L., Tsunematsu, R., Tsuda, M., Sawa, H., Nagashima, K., Nishihara, H., Hatakeyama, S., Nakayama, K., Ladanyi, M., Tanaka, S., Nakayama, KI
• [Journal Article] Crk adaptor protein-induced phosphorylation of Gab1 on tyrosine 307 via Src is important for organization of focal adhesions and enhanced cell migration (2009)
  • Author(s): Watanabe, T., Tsuda, M., Makino, Y., Konstantinou T., Nishihara, H., Majima, T., Minami, A., Feller, SM., Tanaka, S
  • Journal Title: Cell Res 19 Pages: 638-650
• [Journal Article] Integral role of transcription factor 8 in the negative regulation of tumor angiogenesis (2009)
  • Author(s): Inuzuka, T., Tsuda, M., Tanaka, S., Kawaguchi, H. Higashi, Y., Ohba, Y
  • Journal Title: Cancer Res 69 Pages: 1678-1684
• [Journal Article] Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice (2009)
  • Author(s): Miura, M., Ohnishi, N., Tanaka, S., Yanagiya, K., Hatakeyama, M
  • Journal Title: Int J Cancer 125 Pages: 2497-2504
• [Journal Article] Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice (2009)
  • Author(s): Yokota, T., Kinugawa, S., Hirabayashi, K., Matsushima, S., Inoue, N., Ohta, Y., Hamaguchi, S., Sobiri, MA., Ono, T., Suga, T., Kuroda, S., Tanaka, S., Terasaki, F., Okita, K., Tsutsui, H
  • Journal Title: Am J Physiol Heart Circ Physiol 297 Pages: 1069-1077
• [Journal Article] networks for physiological and pathological signaling (2009)
  • Author(s): Birge, RB., Kalodimos, C., Inagaki, F., Tanaka, S. Crk, CrkL adaptor proteins
  • Journal Title: Cell Commun Signal 7 Pages: 13
• [Journal Article] Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methy lguanine-DNA methyltransferase status in glioma (2008)
  • Author(s): Sasai, K., Nodagashira, M., Nishihara, H., Aoyanagi, E., Wang, L., Katoh, M., Murata, J., Ozaki, Y., Ito, T., Fujimoto, S., Kaneko, S., Nagashima, K., Tanaka, S
  • Journal Title: Am. J. Surg. Pathol 32 Pages: 1220-1227
• [Journal Article] Promoter hypomethylation regulates CD133 expression in human gliomas (2008)
  • Author(s): Tabu, K., Sasai, K., Kimura, T., Wang, L., Aoyanagi, E., Kohsaka, S., Tanino, M., Nishihara, H., Tanaka, S
  • Journal Title: Cell Res 18 Pages: 1037-1046
• [Journal Article] PILRαis a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B (2008)
  • Author(s): Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P.G., Lanier, L.L., Arase, H
  • Journal Title: Cell 132 Pages: 935-944
• [Journal Article] Establishment of a luciferase assay-based screening system: fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT (2008)
  • Author(s): Wang, L., Sasai, K., Akagi, T., Tanaka, S
  • Journal Title: Biochem. Biophys, Res, Commun 373 Pages: 392-396
• [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse (2008)
  • Author(s): Ohnishi, N., Yuasa, H., Tanaka, S., Sawa, H., Miura, M., Matsui, A., Higashi, H., Musashi, M., Iwabuchi, K., Suzuki, M., Yamada, G., Azuma, T., Hatakeyama, M
  • Journal Title: Proc. Natl. Acad. Sci. U S A 105 Pages: 1003-1008
• [Journal Article] Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/-mice (2008)
  • Author(s): Mishima, T., Iwabuchi, K., Fujii, S., Tanaka, S., Ogura, H., Watano-Miyata, K., Ishimori, N., Andoh, Y. Nakai, Y., Iwabuchi, C., Ato, M., Kitabatake, A., Tsutsui, H., Onoe, K
  • Journal Title: Int., J. Mol. Med 21 Pages: 181-187
• [Journal Article] Harlequin ichthyosis model mouse reveals alveolar aollapse and severe fetal skin barrier defects (2008)
  • Author(s): Yanagi, T., Akiyama, M., Nishihara, H., Sakai, K. Nishie, W., Tanaka, S., Shimizu, H
  • Journal Title: Human Mol. Genetics 17 Pages: 3075-3083
• [Journal Article] Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK (2007)
  • Author(s): Kobashigawa, Y., Sakai, M., Naito, M., Yokochi, M., Kumeta, H., Makino, Y., Ogura, K., Tanaka, S., Inagaki, F
  • Journal Title: Nature Strct&Mol. Biol 6 Pages: 503-510
• [Journal Article] O6-methylguanine-DNA methyltransferase is downregulated in transformed astrocyte cells: implications for anti-glioma therapies (2007)
  • Author(s): Sasai, K., Akagi, T., Aoyanagi, E., Tabu, K., Kaneko, S., Tanaka, S
  • Journal Title: Mol. Cancer 6 Pages: 36
• [Journal Article] Expression of OLIG2 suppresses the motility of human glial tumor cell line via RhoA activation (2007)
  • Author(s): Tabu, K., Ohba, Y., Suzuki, T., Makino, Y., Ohnish, A., Sakai, M., Watanabe, T., Kimura, T., Tanaka, S., Sawa, H
  • Journal Title: Mol. Cancer Res 5 Pages: 1099-1109
• [Journal Article] Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4 (2007)
  • Author(s): Wang, L., Tabu, K., Kimura, T., Tsuda, M., Linghu, H., Tanino, M., Kaneko, S., Nishihara, H., Tanaka, S
  • Journal Title: Biochem Biophys Res Commun 362 Pages: 976-98
• [Journal Article] Immunohistochemical and Gene Rearrangement Studies of Central Nervous System Lymphomatoid Granulomatosis (2007)
  • Author(s): Nishihara, H., Tateishi, U., Itoh, T., Nagashima, K., Tanaka, S
  • Journal Title: Neuropathology 27 Pages: 413-417
• [Journal Article] Type I interferon prolongs cell cycle progression via p21 WAF1/CIP1 induction in human colon cancer cells (2007)
  • Author(s): Katayama, T., Nakanishi, K., Nishihara, H., Kamiyama, N., Nakagawa, T., Kamiyama, T., Iseki, K., Tanaka, S., Todo, S
  • Journal Title: Int. J. Oncol 31 Pages: 613-620
• [Presentation] 髄膜腫におけるDOCK180の発現の検討 (2009)
  • Author(s): 西原広史、村上普美、木村憲一、佐和弘基、鎌田一、田中伸哉
  • Organizer: 第50回日本神経病理学会
  • Place of Presentation: 高松
  • Year and Date: 20090604-20090606
• [Presentation] 悪性膠腫におけるCD133発現の分子細胞病理学的解析 (2009)
  • Author(s): 椨康一、笹井研、木村太一、谷野美智枝、青柳瑛子、王磊、高阪真路、西原広史、田中伸哉
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20090515-20080517
• [Presentation] GlioblastomaにおけるCD133の発現の免疫組織学的解析 (2009)
  • Author(s): 田中伸哉、大森優子、椨康一、野田頭未歩、青柳瑛子、伊藤民雄、中村博彦、西原広史、笹井研
  • Organizer: 第27回日本脳腫瘍病理学会
  • Place of Presentation: 福岡
  • Year and Date: 20090508-20090509
• [Presentation] OCK180はHodgkin細胞に発現し、細胞の形態制御に重要な役割を果たしている (2009)
  • Author(s): 王磊、西原広史、田中伸哉
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] Gliomaの腫瘍形成能におけるCHD5の役割の検討 (2009)
  • Author(s): 高阪真路、笹井研、谷野美智枝、野田頭未歩、田中伸哉
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] SYT-SSX1トランスジェニックマウスはp53へテロ環境下で滑膜肉腫様腫瘍を発生する (2008)
  • Author(s): 津田真寿美、渡部琢哉、大場雄介、田中伸哉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-20081030
• [Presentation] ヒト腫瘍細胞におけるCD133遺伝子の発現メカニズム (2008)
  • Author(s): 木村太一、笹井研、田賀哲也、田中伸哉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-20081030
• [Presentation] 胸膜中皮腫におけるシグナルアダプター分子CRKの役割の解析 (2008)
  • Author(s): 谷野美智枝、王磊、西原広史、松野吉宏、矢野聖二、曽根三郎、田中伸哉
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 20080615-20080617
• [Presentation] MGMT発現評価は病理組織学的に腫瘍と非腫瘍成分を識別することが重要である (2008)
  • Author(s): 田中伸哉、野田頭未歩、青柳瑛子、加藤正仁、村田純一、伊東民雄、尾崎義丸、藤本真、金子貞夫、西原広史、笹井研、長嶋和郎
  • Organizer: 第26回日本脳腫瘍病理学会
  • Place of Presentation: 東京
  • Year and Date: 20080523-20080524
• [Presentation] 悪性膠腫におけるMGMT発現の解析:免疫染色法とメチル化特異的PCR法の比較. (2008)
  • Author(s): 田中伸哉、野田頭未歩、青柳瑛子、王磊、西原広史、長嶋和郎、笹井研
  • Organizer: 第49回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 20080520-20080522
• [Presentation] 悪性膠腫におけるMGMT発現の病理組織学的解析 (2008)
  • Author(s): 野田頭未歩、青柳瑛子、笹井研、王磊、西原広史、長嶋和郎、田中伸哉
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20080515-20080517
• [Presentation] トランスレーショナル・パソロジーを目指して (2008)
  • Author(s): 田中伸哉
  • Organizer: 第88回北海道医学大会病理分科会・第41回北海道病理談話会
  • Place of Presentation: 札幌
  • Year and Date: 2008-09-20