Mechanism and regulation of gastric carcinogenesis caused by Helicobacter pylori infection

• Project/Area Number: 17013001
• 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: HATAKEYAMA Masanori Hokkaido University, 大学院・医学系研究科, 教授 (40189551)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥140,400,000 (Direct Cost: ¥140,400,000); Fiscal Year 2009: ¥32,200,000 (Direct Cost: ¥32,200,000); Fiscal Year 2008: ¥32,200,000 (Direct Cost: ¥32,200,000); Fiscal Year 2007: ¥26,000,000 (Direct Cost: ¥26,000,000); Fiscal Year 2006: ¥26,000,000 (Direct Cost: ¥26,000,000); Fiscal Year 2005: ¥24,000,000 (Direct Cost: ¥24,000,000)
• Keywords: ヘリコバクター・ピロリ / CagA / トランスジェニックマウス / 胃がん / 血液がん / 胃癌 / 血液癌 / 細菌性癌タンパク / SHP-2 / PAR1b / MARK2 / へリコバクター・ピロリ / β-catenin / 腸上皮化生 / Cdx1 / 多量体化 / FAK / チロシンリン酸化 / 脱リン酸化 / NFAT / VacA

Research Abstract

We identified that, upon delivery into host gastric epithelial cells, Helicobacter pylori virulence factor CagA binds to a human oncoprotein SHP-2 phosphatase and PAR1/MARK cell polarity regulator to perturb their activities, thereby causing cellular dysfunction that lead to malignant transformation. We also generated transgenic mice that express the H. pylori cagA gene and confirmed that CagA is the first bacterium-derived oncoprotein. Furthermore, we delineated the relationship between the structural polymorphism and the degree of oncogenic potential of CagA.

Research Products

• [Journal Article] Helicobacter pylor CagA activates NF-kB by targeting TAK1 for TRAF6-mediated K63-ubiquitination. (2009)
  • Author(s): Lamb, A., Yang, X-D., Nicole, Tsang., Y-H., Li, J-D., Higashi, H., Hatakeyama, M., Peek, R.M., Blanke, S. R, Chen, L-F.
  • Journal Title: EMBO Rep. 10 Pages: 1242-1249
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Role of Partitioning - defective 1/Microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA. (2009)
  • Author(s): Lu, H., Murata-Kamiya, N., Saito, Y, Hatakeyama, M.
  • Journal Title: J. Biol. Chem. 284 Pages: 23024-23036
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability. (2009)
  • Author(s): Umeda, M., Murata-Kamiya, N., Saito Y., Ohba, Y., Takahashi, M, Hatakeyama, M.
  • Journal Title: J. Biol. Chem. 284 Pages: 22166-22172
  • Peer Reviewed
• [Journal Article] Stability of Helicobacter pylori CagA oncoprotein in human gastric epithelial cells. (2009)
  • Author(s): Ishikawa, S., Ohta, T, Hatakeyama, M.
  • Journal Title: FEBS Letters 583 Pages: 2414-2418
  • Peer Reviewed
• [Journal Article] Helicobacter pylori and gastric carcinogenesis. (2009)
  • Author(s): Hatakeyama, M.
  • Journal Title: J. Gastroenterol. 44 Pages: 239-248
  • NAID: 10025173914
  • Peer Reviewed
• [Journal Article] Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway. (2009)
  • Author(s): Nakayama, M., Hisatsune, J., Yamasaki, E., Isomoto, H., Kurazono, H., Hatakeyama, M., Azuma, T., Yamaoka, Y., Yahiro, K., Moss, J, Hirayama, T.
  • Journal Title: J. Biol. Chem. 284 Pages: 1612-1619
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA activates NF-kB by targeting TAK1 for TRAF6-mediated K63-ubiauitination (2009)
  • Author(s): Lamb, A.
  • Journal Title: EMBO Rep. 10 Pages: 1242-1249
  • Peer Reviewed
• [Journal Article] Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice (2009)
  • Author(s): Miura, M.
  • Journal Title: Int.J.Cancer. 125 Pages: 2497-2504
  • Peer Reviewed
• [Journal Article] Role of Partitioning-defective 1/Microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA.J.Biol (2009)
  • Author(s): Lu, H.
  • Journal Title: J.Biol.Chem. 284 Pages: 23024-23036
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability (2009)
  • Author(s): Umeda, M.
  • Journal Title: J.Biol.Chem. 284 Pages: 22166-22172
  • Peer Reviewed
• [Journal Article] Stability of Helicobacter pylori CagA oncoprotein in human gastric epithelial cells (2009)
  • Author(s): Ishikawa, S.
  • Journal Title: FEBS Letters 583 Pages: 2414-2418
  • Peer Reviewed
• [Journal Article] Helicobacter pylori and gastric carcinogenesis (2009)
  • Author(s): Hatakeyama, M.
  • Journal Title: J Gastroenterol. 44 Pages: 239-248
  • NAID: 10025173914
  • Peer Reviewed
• [Journal Article] Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway (2009)
  • Author(s): Nakayama, M.
  • Journal Title: J.Biol.Chem. 284 Pages: 1612-1619
  • Peer Reviewed
• [Journal Article] Helicobacter pylori による胃発癌機構 (2009)
  • Author(s): 林剛瑠
  • Journal Title: 蛋白質核酸酵素 54(No.8) Pages: 1009-1013
• [Journal Article] Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. (2008)
  • Author(s): Hatakeyama, M.
  • Journal Title: Oncogene 27 Pages: 7047-7054
  • Peer Reviewed
• [Journal Article] Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA. (2008)
  • Author(s): Lu, H., Saito, Y., Umeda, M., Murata-Kamiya, N., Zhang, H., Higashi, H, Hatakeyama, M.
  • Journal Title: Cancer Science 99 Pages: 2004-2011
  • NAID: 10024012093
  • Peer Reviewed
• [Journal Article] Anti-tumor activity of ESX1 on cancer cells harboring oncogenic K-ras mutation. (2008)
  • Author(s): Nakajima, J., Ishikawa, S., Hamada, J., Yanagihara, M., Koike, T, Hatakeyama, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 370 Pages: 189-194
  • Peer Reviewed
• [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. (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: Natl. Acad. Sci. USA 105 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] SagA of CagA in Helicobacter pylori pathogenesis. (2008)
  • Author(s): Hatakeyama, M.
  • Journal Title: Cur. Opin. Microbiol. 11 Pages: 30-37
  • Peer Reviewed
• [Journal Article] Isolation of a distinct class of gain-of-function SHP-2 muntants with oncogenic RAS-like transforming activity from solid tumors. (2008)
  • Author(s): Miyamoto, D., Miyamoto, M., Takahashi, A., Yomogita, Y., Higashi, H., Kondo, S, Hatakeyama, M.
  • Journal Title: Oncogene 27 Pages: 3508-3515
  • Peer Reviewed
• [Journal Article] Deregulation of b-catenin signal by Helicobacter pylori CagA requires the CagA - multimerization sequence. (2008)
  • Author(s): Kurashima, Y., Murata-Kamiya, N., Kikuchi, K., Higashi, H., Azuma, T., Kondo, S, Hatakeyama, M.
  • Journal Title: International Journal of Cancer 122 Pages: 823-831
  • Peer Reviewed
• [Journal Article] H. pylori CagAによる細胞がん化のメカニズム (2008)
  • Author(s): 畠山昌則.
  • Journal Title: 医学のあゆみ 224 Pages: 704-710
• [Journal Article] Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA (2008)
  • Author(s): Hatakeyama, M.
  • Journal Title: Oncogene 27 Pages: 7047-7054
  • Peer Reviewed
• [Journal Article] Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CaeA (2008)
  • Author(s): Lu, H.
  • Journal Title: Cancer Science 99 Pages: 2004-2011
  • Peer Reviewed
• [Journal Article] Anti-tumor activity of ESXl on cancer cells harboring oncogenic K-ras mutation (2008)
  • Author(s): Nakajima, J.
  • Journal Title: Biochem. Biophys. Res. Commun 370 Pages: 189-194
  • Peer Reviewed
• [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neonlasms in mouse (2008)
  • Author(s): Ohnishi, N.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] SagA of CagA in Helicobacter pylori pathogenesis (2008)
  • Author(s): Hatakeyama, M.
  • Journal Title: Cur. Opin. Microbiol 11 Pages: 30-37
  • Peer Reviewed
• [Journal Article] Isolation of a distinct class of gain-of-function SHP-2 muntants with oncogenic RAS-like transforming activity from solid tumors (2008)
  • Author(s): Miyamoto, D.
  • Journal Title: Oncogene 27 Pages: 3508-3515
  • Peer Reviewed
• [Journal Article] Deregulation of β-catenin signal by Helicobacter pylori CagA requires the CaeA-multimerization seauence (2008)
  • Author(s): Kurashima, Y.
  • Journal Title: International Journal of Cancer 122 Pages: 823-831
  • Peer Reviewed
• [Journal Article] ピロリ菌がつくるタンパク質の発がん活性を証明 (2008)
  • Author(s): 畠山昌則
  • Journal Title: 医学のあゆみ 224 Pages: 704-710
• [Journal Article] 胃がん発症におけるHelicobacter pylori CagAの意義 (2008)
  • Author(s): 齊藤康弘
  • Journal Title: 血液・腫瘍科 56 Pages: 219-225
• [Journal Article] H.pylori除菌と3剤併用療法 (2008)
  • Author(s): 菊地健司
  • Journal Title: 医薬ジャーナル 44,S-1 Pages: 263-268
• [Journal Article] Anti-tumor activity of ESX1 on cancer cells harboring oncogenic K-ras mutation. (2008)
  • Author(s): Nakajima, J.
  • Journal Title: Biochem. Biophys. Res. Commun. (In press)
  • Peer Reviewed
• [Journal Article] Isolation of a distinct class of gain-of-function SHP-2 muntants with oncogenic RAS-like transforming activity from solid tumors. (2008)
  • Author(s): Miyamoto, D.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. (2008)
  • Author(s): Ohnishi, N.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] H.pylori除菌と3剤併用療法。 (2008)
  • Author(s): 菊地健司
  • Journal Title: 医薬ジャーナル 44 Pages: 263-268
• [Journal Article] 胃がん発症におけるHelicobacter pylori CagAの意義。 (2008)
  • Author(s): 齊藤康弘
  • Journal Title: 血液・腫瘍科 56 Pages: 219-225
• [Journal Article] H.pylori CagAによる細胞癌化ノメカニズム。 (2008)
  • Author(s): 畠山昌則
  • Journal Title: 医学のあゆみ 224 Pages: 704-710
• [Journal Article] ピロリ菌がつくるタンパク質の発がん活性を証明。 (2008)
  • Author(s): 畠山昌則
  • Journal Title: Medical Bio (March) Pages: 14-15
• [Journal Article] Helicobacter pylori CagA targets PAR1 / MARK kinase to disrupt epithelial cell polarity. (2007)
  • Author(s): Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., Lu, H., Ohnishi, N., Azuma, T., Suzuki, A., Ohno, S, Hatakeyama, M.
  • Journal Title: Nature 447 Pages: 330-333
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA interacts with E-cadherin and deregulates the b-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. (2007)
  • Author(s): Murata-Kamiya, N., Kurashima, Y., Teishikata, Y., Yamahashi, Y., Saito, Y., Higashi, H., Aburatani, H., Akiyama, T., Peek, R.M., Jr., Azuma, T, Hatakeyama, M.
  • Journal Title: Oncogene 26 Pages: 4617-4626
  • Peer Reviewed
• [Journal Article] ヘリコバクター・ピロリCagAによる上皮細胞極性破壊と細胞がん化のカップリング (2007)
  • Author(s): 畠山昌則.
  • Journal Title: 細胞工学 27 Pages: 172-177
• [Journal Article] ヘリコバクター・ピロリと胃がん (2007)
  • Author(s): 畠山昌則.
  • Journal Title: 日本消化器病学会雑誌-総説 104 Pages: 635-643
• [Journal Article] Deregulation of β-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. (2007)
  • Author(s): Kurashima, Y.
  • Journal Title: International Journal of Cancer 122 Pages: 823-831
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. (2007)
  • Author(s): Saadat, I.
  • Journal Title: Nature 447 Pages: 330-333
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. (2007)
  • Author(s): Murata-Kamiya, N.
  • Journal Title: Oncogene 26 Pages: 4617-4626
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagAはPAR1b/MARK2キナーゼを標的として上皮細胞の極性を破壊する。 (2007)
  • Author(s): 紙谷尚子
  • Journal Title: 分子消化器病学 4 Pages: 114-118
• [Journal Article] ヘリコバクター・ピロリCagAによる上皮細胞極性破壊と細胞癌化のカップリング。 (2007)
  • Author(s): 畠山昌則
  • Journal Title: 細胞工学 27 Pages: 172-177
  • NAID: 40015848589
• [Journal Article] ヘリコバクター・ピロリと胃癌。 (2007)
  • Author(s): 畠山昌則
  • Journal Title: 日本消化器病学会雑誌-総説 104 Pages: 635-643
  • NAID: 10019545240
• [Journal Article] Structural basis and functional consequence of Helicobacter pylori CagA multimerization in Cells. (2006)
  • Author(s): Ren, S., Higashi, H., Lu, H., Azuma, T, Hatakeyama, M.
  • Journal Title: J. Biol. Chem. 281 Pages: 32344-32352
  • Peer Reviewed
• [Journal Article] The role of Helicobacter pylori CagA in gastric carcinogenesis. (2006)
  • Author(s): Hatakeyama, M.
  • Journal Title: Int. J. Hematol. 84 Pages: 301-308
  • NAID: 10019259495
  • Peer Reviewed
• [Journal Article] Development of a novel method to detect Helicobacter pylori cagA genotype from paraffin - embedded materials: comparison between patients with duodenal ulcer and gastric cancer in young Japanese. (2006)
  • Author(s): Ueda, H., Ito, M., Eguchi, H., Tanaka, S., Yoshihara, M., Haruma, K., Hatakeyama, M, Chayama, K.
  • Journal Title: Digestion 73 Pages: 47-53
  • Peer Reviewed
• [Journal Article] Pathogenesis of Helicobacter pylori infection. (2006)
  • Author(s): Hatakeyama, M, Brzozowski, T.
  • Journal Title: Helicobacter 11,Suppl1 Pages: 14-20
  • Peer Reviewed
• [Journal Article] Influence of EPIYA - repeat polymorphism on the phosphorylation- dependent biological activity of Helicobacter pylori CagA. (2006)
  • Author(s): Naito, M., Yamazaki, T., Tsutsumi, R., Higashi, H., Onoe, K., Yamazaki, S., Azuma, T, Hatakeyama, M.
  • Journal Title: Gastroenterology 130 Pages: 1181-1190
  • NAID: 120000953487
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA-a bacterial intruder conspiring gastric carcinogenesis. (2006)
  • Author(s): Hatakeyama, M.
  • Journal Title: Int. J. Cancer 119 Pages: 1217-1223
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. (2006)
  • Author(s): Tsutsumi, R., Takahashi, A., Azuma, A., Higashi, H, Hatakeyama, M.
  • Journal Title: Mol. Cell. Biol. 26 Pages: 261-276
  • NAID: 120000957433
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA associates with E-cadherin and deregulates β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. (2006)
  • Author(s): Murata-Kamiya, N.
  • Journal Title: Oncogene (in press)
• [Journal Article] Structural basis and functional consequence of Helicobacter pylori CagA multimerization in cells. (2006)
  • Author(s): Ren, S.
  • Journal Title: J. Biol. Chem. 281 Pages: 32344-32352
• [Journal Article] Development of a novel method to detect Helicobacter pylori cagA genotype from paraffin-embedded materials : comparison between patients with duodenal ulcer and gastric cancer in young Japanese. (2006)
  • Author(s): Ueda, H.
  • Journal Title: Digestion 732 Pages: 47-53
• [Journal Article] Pathogenesis of Helicobacter pylori infection. (2006)
  • Author(s): Hatakeyama, M.
  • Journal Title: Helicobacter 11
• [Journal Article] Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. (2006)
  • Author(s): Naito, M.
  • Journal Title: Gastroenterolory 130 Pages: 1181-1190
• [Journal Article] Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. (2006)
  • Author(s): Tsutsumi, R.
  • Journal Title: Mol. Cell. Biol. 26 Pages: 261-276
• [Journal Article] ピロリ菌の生態と最新研究。 (2006)
  • Author(s): 畠山 昌則
  • Journal Title: 化学 61 Pages: 18-20
• [Journal Article] ピロリ菌と胃潰瘍・胃癌-検査とのかかわり。 (2006)
  • Author(s): 湯浅 眸
  • Journal Title: 検査と技術 34 Pages: 802-805
• [Journal Article] ヘリコバクター・ピロリ感染と胃癌。 (2006)
  • Author(s): 畠山 昌則
  • Journal Title: Cancer Frontier 8 Pages: 98-106
• [Journal Article] ヘリコバクター・ピロリ病原因子CagAと胃癌。 (2006)
  • Author(s): 畠山 昌則
  • Journal Title: 化学と生物 44 Pages: 681-687
  • NAID: 10018252529
• [Journal Article] Helicobacter pylori感染と胃癌。 (2006)
  • Author(s): 畠山 昌則
  • Journal Title: Bio Clinica 21 Pages: 1064-1069
• [Journal Article] Influence of EPIYA-repeat Polymorphism on the Phosphorylation-dependent Biological Activity of Helicobacter pylori CagA. (2006)
  • Author(s): Naito, M.
  • Journal Title: Gastroenterolory (in press)
• [Journal Article] Helicobacter pylori CagA-a bacterial intruder conspiring gastric carcinogenesis. (2006)
  • Author(s): Hatakeyama, M.
  • Journal Title: Int.J.Cancer (in press)
• [Journal Article] Focal Adhesion Kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. (2006)
  • Author(s): Tsutsumi, R.
  • Journal Title: Mol.Cell.Biol. 26 Pages: 261-276
• [Journal Article] Helicobacter pylori CagA - a new paradigm for bacterial carcinogenesis. (2005)
  • Author(s): Hatakeyama, M., Higashi, H.
  • Journal Title: Cancer Sci. 96 Pages: 835-843
  • NAID: 10017103932
  • Peer Reviewed
• [Journal Article] Downregulation of cyclin-dependent kinase inhibitor; p57(kip2), is involved in the cell cycle progression of vascular smooth muscle cells. (2005)
  • Author(s): Nakano, N., Urasawa, K., Takagi, Y., Saito, T., Kaneta, S., Ishikawa, S., Higashi, H., Tsutsui, H., Hatakeyama, M, Kitabatake, A.
  • Journal Title: Biochem. Biophys. Res. Commun. 338 Pages: 1661-1667
  • Peer Reviewed
• [Journal Article] Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene. (2005)
  • Author(s): Yanagihara, M., Ishikawa, S., Naito, M., Nakajima, J., Aburatani, H, Hatakeyama, M.
  • Journal Title: Oncogene 24 Pages: 5878-5887
  • Peer Reviewed
• [Journal Article] Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. (2005)
  • Author(s): Yokoyama, K., Higashi, H., Ishikawa, S., Fujii, Y., Kondo, S., Kato, H., Azuma, T., Wada, A., Hirayama, T., Aburatani, H, Hatakeyama, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 9661-9666
  • Peer Reviewed
• [Journal Article] EPIYA motif is a membrane-targeting singnal of Helicobacter pylori virulence factor CagA in mammalian cells. (2005)
  • Author(s): Higashi, H., Yokoyama, K., Fujii, Y., Ren, S., Yuasa, H., Saadat, I., Murata-Kamiya, N., Azuma, T, Hatakeyama, M.
  • Journal Title: J. Biol. Chem. 280 Pages: 23130-23137
  • Peer Reviewed
• [Journal Article] Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc. (2005)
  • Author(s): Franco, A.T., Israel, D.A., Washington, M.K., Krishna, U., Fox, J.G., Rogers, A.B., Neish, A.S., Collier-Hyams, L., Perez-Perez, G.I., Hatakeyama, M., Whitehead, R., gaus, K., O'brien, D.P., Romero-Gallo, J., Peek, R.M., Jr.
  • Journal Title: Natl. Acad. Sci. USA 102 Pages: 10646-10651
  • Peer Reviewed
• [Journal Article] Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan. (2005)
  • Author(s): Yamazaki, S., Yamakawa, A., Okuda, T., Ohtani, M., Suto, H., Ito, Y., Yamazaki, Y., Keida, Y., Higashi, H., Hatakeyama, M, Azuma, T.
  • Journal Title: J. Clin. Microbiol. 43 Pages: 3906-3916
  • Peer Reviewed
• [Journal Article] Identification of Helicobacter pylori and the cagA genotype in gastric biopsies using higly sensitive real-time PCR as a new diagnostic tool. (2005)
  • Author(s): Yamazaki, S., Kato, S., Matsukura, N., Ohtani, M., Ito, Y., Suto, H., Yamazaki, Y., Yamakawa, A., Tokudome, S., Higashi, H., Hatakeyama, M, Azuma, T.
  • Journal Title: FEMS Immunol. Med. Microbiol. 44 Pages: 261-268
  • Peer Reviewed
• [Journal Article] H. pylori感染による胃発がん機序 (2005)
  • Author(s): 畠山昌則
  • Journal Title: 消化器科 41 Pages: 389-397
• [Journal Article] Helicobacter pylori CagA -SHP-2相互作用と胃がん (2005)
  • Author(s): 畠山昌則
  • Journal Title: 日本臨床 63,Suppl11 Pages: 48-52
• [Journal Article] Helicobacter pylori CagA-a new paradigm for bacterial carcinogenesis. (2005)
  • Author(s): Hatakeyama, M.
  • Journal Title: Cancer Sci. 96 Pages: 835-843
  • NAID: 10017103932
• [Journal Article] Downregulation of cyclin-dependent kinase inhibitor ; p57(kip2), is involved in the cell cycle progression of vascular smooth muscle cells. (2005)
  • Author(s): Nakano, N.
  • Journal Title: Biochem.Biophys.Res.Commun. 338 Pages: 1661-1667
• [Journal Article] Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene. (2005)
  • Author(s): Yanagihara, M.
  • Journal Title: Oncogene 24 Pages: 5878-5887
• [Journal Article] Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NEAT signaling pathway in gastric epithelial cells. (2005)
  • Author(s): Yokoyama, K.
  • Journal Title: Proc.Natl.Acad.Sci.USA 102 Pages: 9661-9666
• [Journal Article] EPIYA motif is a membrane-targeting singnal of Helicobacter pylori virulence factor CagA in mammalian cells. (2005)
  • Author(s): Higashi, H.
  • Journal Title: J.Biol.Chem. 280 Pages: 23130-23137
• [Journal Article] Activation of beta-catenin by carcinogenic Helicobacter pylori. (2005)
  • Author(s): Franco, A.T.
  • Journal Title: Natl.Acad.Sci.USA 102 Pages: 10646-10651
• [Journal Article] Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan. (2005)
  • Author(s): Yamazaki, S.
  • Journal Title: J.Clin.Microbiol. 43 Pages: 3906-3916
• [Journal Article] Identification of Helicobacter pylori and the cagA genotype in gastric biopsies using higly sensitive real-time PCR as a new diagnostic tool. (2005)
  • Author(s): Yamazaki, S.
  • Journal Title: FEMS Immunol.Med.Microbiol. 44 Pages: 261-268
• [Journal Article] ヘリコバクター・ピロリの分子生物学。 (2005)
  • Author(s): 紙谷 尚子
  • Journal Title: 化学療法の領域 21 Pages: 25-31
• [Journal Article] Helicobacter pylori感染による胃発がん機構。 (2005)
  • Author(s): 高橋 昌史
  • Journal Title: がん分子標的治療 3 Pages: 74-79
• [Journal Article] 胃癌発症におけるヘリコバクター・ピロリ菌病原因子CagAの役割。 (2005)
  • Author(s): 内藤 正規
  • Journal Title: Cancer Frontier 7 Pages: 144-149
• [Journal Article] Helicobacter pylori CagAとSHP-2チロシンホスファターゼ。 (2005)
  • Author(s): 堤 良平
  • Journal Title: 生化学 77 Pages: 1269-1273
• [Journal Article] Helicobacter pylori感染と胃がん。 (2005)
  • Author(s): 畠山 昌則
  • Journal Title: 分子細胞治療 4 Pages: 373-379
• [Journal Article] Helicobacter pylori CagA-SHP-2相互作用と胃癌。 (2005)
  • Author(s): 畠山 昌則
  • Journal Title: 日本臨床 63 Pages: 48-52
• [Journal Article] Helicobacter pylori and gastric carcinogenesis
  • Author(s): Hatakeyama, M.
  • Journal Title: I Gastroenterol (in press)
  • NAID: 10025173914
  • Peer Reviewed
• [Journal Article] Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway
  • Author(s): Nakayama, M.
  • Journal Title: J. Biol.Chem. (in press)
  • Peer Reviewed
• [Presentation] Oncogenic mechanism of Helicobacter pylori CagA (2010)
  • Author(s): 畠山昌則
  • Organizer: ドイツ衛生学・微生物学会(DGHM)
  • Place of Presentation: Convention Center Hanover, Hanover, Germany.
  • Year and Date: 2010-03-30
• [Presentation] New Approaches to Cancer Immunotherapy (2010)
  • Author(s): 畠山昌則
  • Organizer: 日米がん合同会議(JCA-AACR)
  • Place of Presentation: Hilton Waikoloa Village, Waikoloa, Hawaii.
  • Year and Date: 2010-02-05
• [Presentation] New Approaches to Cancer Immunotherapy (2010)
  • Author(s): 畠山昌則
  • Organizer: 日米癌合同会議(JCA-AACR)
  • Place of Presentation: Waikoloa, Hawaii, U.S.A.Hilton Waikoloa Village
• [Presentation] Oncogenic Actions of the Helicobacter pylori CagA protein (2010)
  • Author(s): 畠山昌則
  • Organizer: 第2回北海道大学遺伝子病制御研究所感染癌研究センター国際シンポジウム
  • Place of Presentation: 札幌、北大学術交流会館
• [Presentation] Oncogenic mechanism of Helicobacter pylori CagA (2010)
  • Author(s): 畠山昌則
  • Organizer: ドイツ衛生学・微生物学会(DGHM)
  • Place of Presentation: Hanover, Germany, Convention Center Hanover
• [Presentation] Overview of research on cancer, infection and immunity (2009)
  • Author(s): 畠山昌則
  • Organizer: Max-Planck Society-University of Tokyo Graduate School of Medicine Joint Symposium
  • Place of Presentation: 東京、東京大学
  • Year and Date: 2009-12-03
• [Presentation] Animal Model of Carcinogenesis (2009)
  • Author(s): 畠山昌則
  • Organizer: 2nd Gyoungnam Regional Cancer Center Symposium
  • Place of Presentation: Gyeongsang National University Hospital, Jinju, Krea.
  • Year and Date: 2009-11-19
• [Presentation] Helicobacter pylori CagA-a new paradigm for oncoprotcins (2009)
  • Author(s): 畠山昌則
  • Organizer: 自治医科大学国隙シンポジウム
  • Place of Presentation: 栃木、自治医科大学
  • Year and Date: 2009-11-07
• [Presentation] Gastric cancer - a paradigm of bacterial carcinogenesis (2009)
  • Author(s): 畠山昌則
  • Organizer: French- Japanese Workshop in Life Sciences
  • Place of Presentation: CNRS. Campas Gerard-Megie, Paris, France.
  • Year and Date: 2009-09-22
• [Presentation] Helicobacter pylori CagA-the first bacterial oncoprotein to be discoverd (2009)
  • Author(s): 畠山昌則
  • Organizer: 15^<th> International Workshop on Campylobacter, Helicobacter and Related Organisms(CHRO2009)
  • Place of Presentation: 新潟、朱鷺メッセコンベンションセンター
  • Year and Date: 2009-09-02
• [Presentation] ピロリ菌と胃がん (2009)
  • Author(s): 畠山昌則
  • Organizer: 第7回化学イノベーションシンポジウム
  • Place of Presentation: 札幌、共済ホール
  • Year and Date: 2009-08-08
• [Presentation] ピロリ菌感染と胃癌 (2009)
  • Author(s): 畠山昌則
  • Organizer: 第19回日本産婦人科・新生児血液学会
  • Place of Presentation: 札幌、北大学術交流会館
  • Year and Date: 2009-05-21
• [Presentation] Oncogenic mechanisms of Helicobacter pylori CagA (2009)
  • Author(s): Hatakeyama, M.
  • Organizer: The G-COE First International Symposium
  • Place of Presentation: 神戸市、神戸大学医学部
  • Year and Date: 2009-03-23
• [Presentation] Bifunctional role of Helicobacter pylori CagA as an oncoprotein (2009)
  • Author(s): 畠山昌則
  • Organizer: 第29回札幌がんセミナー国際シンポジウム
  • Place of Presentation: 札幌、北大学術交流会館
• [Presentation] Gastric cancer-a paradigm of bacterial carcinogenesis (2009)
  • Author(s): 畠山昌則
  • Organizer: French-Japanese Workshop in Life Sciences
  • Place of Presentation: Paris, France, CNRS.Campas Gerard-Megie
• [Presentation] 胃がん:基礎から臨床に至るその最前線 (2009)
  • Author(s): 畠山昌則
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] ピロリ菌感染と胃がん (2009)
  • Author(s): 畠山昌則
  • Organizer: 第14回遺伝子実験施設セミナー
  • Place of Presentation: 熊本、熊本大学
• [Presentation] 発がんの新しい分子基盤 (2009)
  • Author(s): 畠山昌則
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] ヘリコバクター・ピロリ感染と胃がん (2009)
  • Author(s): 畠山昌則
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] Does cag cause cancer and if so how? (2008)
  • Author(s): 畠山昌則
  • Organizer: UEGW Vienna 2008/16th United European gastroenterology Week
  • Place of Presentation: Austria Center Vienna, Vienna, Austria.
  • Year and Date: 2008-10-21
• [Presentation] The role of SHP2 phosphatase in H. pylori-mediated gastric carcinogenesis (2008)
  • Author(s): 畠山昌則
  • Organizer: 2008 FASEB Summer Research Conferences
  • Place of Presentation: Snowmass Village, Colorado, USA.
  • Year and Date: 2008-07-15
• [Presentation] The role of SHP2 phosphatase in H. pylori-mediated gastric carcinogenesis (2008)
  • Author(s): 畠山昌則
  • Organizer: IMBA主催生物学セミナーシリーズ
  • Place of Presentation: Vienna Biocenter, Vienna, Austria.
  • Year and Date: 2008-06-12
• [Presentation] ピロリ菌感染症としての胃がん (2008)
  • Author(s): 畠山昌則
  • Organizer: 第3回学習院大学生命科学シンポジウム
  • Place of Presentation: 東京,学習院大学
  • Year and Date: 2008-05-24
• [Presentation] Helicobacter pylori and molecular pathogenesis (2008)
  • Author(s): 畠山昌則
  • Organizer: AACR Annual meeting 2008
  • Place of Presentation: San Diego convention center, San Diego, USA.
  • Year and Date: 2008-04-14
• [Presentation] Gastric Cancer as a Bacterial Disease (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: 未来創薬・医療イノベーション拠点形成シンポジウム
  • Place of Presentation: 北大・学術交流会館
  • Year and Date: 2008-03-14
• [Presentation] H. pylori and gastric carcinogenesis (2008)
  • Author(s): 畠山昌則
  • Organizer: The Asia - Africa International Network Symposium of JSPS Asia and Africa Science Platform Program and The Fourth LiverCare Center Symposium
  • Place of Presentation: Charoen Thani Hotel, Khon Kaen, Thailand.
  • Year and Date: 2008-02-20
• [Presentation] Cellular targets of Helicobacter pylori CagA in gastric carcinogenesis (2008)
  • Author(s): 畠山 昌則
  • Organizer: 金沢がん生物学国際シンポシウム2008
  • Place of Presentation: 金沢大学医学部
  • Year and Date: 2008-01-24
• [Presentation] The role of SHP-2 tyrosine phosphatase in human cancers (2008)
  • Author(s): 畠山昌則
  • Organizer: 第31回日本分子生物学会年会・第81回日本生鱈学会大会合同大会
  • Place of Presentation: 神戸市、神戸国際会議場
• [Presentation] SHP-2 phosphatase and human cancer (2008)
  • Author(s): Hatakyama, M.
  • Organizer: 8^<th> International Conference on Protein Phosphatase
  • Place of Presentation: 前橋市、前橋テレサ
• [Presentation] H.pyloriと胃発がん (2008)
  • Author(s): 畠山昌則
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市、名古屋国際会議場
• [Presentation] Does cag cause cancer and if so how? (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: UEGW Vienna 2008/16th United European gastroenterology Week
  • Place of Presentation: Vienna, Austria, Austria Center Vienna
• [Presentation] The role of SHP2 phosphatase in H.pylori-mediated gastric carcinogenesis (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: 2008 FASEB Summer Research Conferences
  • Place of Presentation: Colorado, USA, Snowmass Village
• [Presentation] 細菌性癌タンパク質としてのピロリ菌CagA (2008)
  • Author(s): 畠山昌則
  • Organizer: Joint Conference in Sapporo 2008
  • Place of Presentation: 札幌市、北大学術交流会館
• [Presentation] The role of SHP2 phosphatase in H.pylori-mediated gastric carcinogenesis (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: IMBA主催生物学セミナーシリーズ
  • Place of Presentation: Vienna, Austria, Vienna Biocenter
• [Presentation] Helicobacter pylori and molecular pathogenesis (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: AACR Annual meeting 2008
  • Place of Presentation: USA, San Diego convention center
• [Presentation] H. pylori and gastric carcinogenesis (2008)
  • Author(s): Hatakeyama, M.
  • Organizer: JSPS Asia Africa Science Platforom Program and The Fourth LiverCare Center Symposium
  • Place of Presentation: Charoen Thani Princess Hotel, Khon Kaen, Thailand
• [Presentation] Disruption of epithelial cell polarity by Helicobacter pylori virulence factor CAgA (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: International Symposium on Cell Polarity System and Future Medicine
  • Place of Presentation: 湘南国際村・Shonan Village center
  • Year and Date: 2007-12-03
• [Presentation] Microbial-host interactions in infectious cancer (2007)
  • Author(s): 畠山昌則
  • Organizer: International Symposium -Dysregulation of cell Communication in immune and Neuronal Cells
  • Place of Presentation: Otto von Guericke University, Magdeburg, Germany.
  • Year and Date: 2007-11-29
• [Presentation] The role of Helicobacter pylori CagA in gastric carcinogenesis (2007)
  • Author(s): 畠山昌則
  • Organizer: Seoul International Digestive Disease Symposium 2007(SIDDS 2007)
  • Place of Presentation: Seoul University, Seoul, Korea.
  • Year and Date: 2007-11-22
• [Presentation] The role of Helicobacter pylori CagA in gastric carcinogenesis (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: Seoul International Digestive Disease Symposium 2007
  • Place of Presentation: Seoul National University,Korea
  • Year and Date: 2007-11-22
• [Presentation] Oncogenic protenital of the Helicobacter pylori CagA (2007)
  • Author(s): 畠山昌則
  • Organizer: Seoul International Digestive Disease Symposium 2007(SIDDS 2007)
  • Place of Presentation: Seoul University, Seoul, Korea.
  • Year and Date: 2007-11-21
• [Presentation] Oncogenic protenital of the Helicobacter pylori CagA (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: Seoul International Digestive Disease Symposium 2007
  • Place of Presentation: Seoul National University,Korea
  • Year and Date: 2007-11-21
• [Presentation] Oncogenic mechnism of Helicobacter pylori CagA (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: The 14th Seoul International Cancer Symposium
  • Place of Presentation: Seoul National University,Korea
  • Year and Date: 2007-11-19
• [Presentation] H.pylori による胃粘膜破壊の分子機構 (2007)
  • Author(s): 畠山 昌則
  • Organizer: 第19回広島ヘリコバクター研究会
  • Place of Presentation: 広島大学医学部
  • Year and Date: 2007-10-02
• [Presentation] The role of Helicobacter pylori CagA in gastric carcinogenesis (2007)
  • Author(s): 畠山昌則
  • Organizer: The 19th FAOBMB Seoul Conference
  • Place of Presentation: COEX Center in Seoul, Seoul, Korea.
  • Year and Date: 2007-05-29
• [Presentation] The role of Helicobacter pylori CagA in gastric carcinogenesis (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: The 19th FAOBMB Seoul Conference
  • Place of Presentation: COEX Center,Seoul,Korea
  • Year and Date: 2007-05-29
• [Presentation] Disruption of epithelial cell polarity by Helicobacter pylori virulence factor CagA (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: BMB 2007Symposium
  • Place of Presentation: パシフィコ横浜
• [Presentation] Microbial-host interactions in infectious cancer (2007)
  • Author(s): Hatakeyama, M.
  • Organizer: International Symposium of the DFG graduate program 1167
  • Place of Presentation: Otto von Guericke University,Magdeburg,Germany
• [Presentation] Activation of β-catenin signal by Helicobacter pylori CagA (2006)
  • Author(s): 畠山昌則
  • Organizer: European Helicobacter Study group International Workshop: Microbiological Aspects and Virulence Factors
  • Place of Presentation: ブロツワフ大学講堂, Wroclaw, Poland.
  • Year and Date: 2006-09-09
• [Presentation] Reciprocal regulation of NFAT transcription factors by the two major Helicobacter pylori virulence factors, CagA and VacA (2005)
  • Author(s): 畠山昌則
  • Organizer: European Helicobacter Study group International Workshop
  • Place of Presentation: Copenhagen, Denmark.
  • Year and Date: 2005-10-14
• [Book] バイオとナノの融合II新生命科学の応用(第22章) (2007)
  • Author(s): 畠山昌則
  • Publisher: 北海道大学発行
• [Book] バイオとナノの融合II新生命科学の応用 (2007)
  • Author(s): 畠山 昌則
  • Total Pages: 26
  • Publisher: 北海道大学
• [Book] 別冊・医学のあゆみ消化管疾患Ver. 3-state of arts. I.(消化管(食道・胃・腸)) (2006)
  • Author(s): 畠山昌則
  • Publisher: 医歯薬出版(株)
• [Book] がん研究の今-1.(笹月健彦、野田哲生編, 発がんの分子機構と防御) (2006)
  • Author(s): 畠山昌則
  • Publisher: 東大出版会
• [Book] 別冊・医学のあゆみ 消化管疾患Ver.3-state of arts.I. (2006)
  • Author(s): 畠山 昌則
  • Total Pages: 3
  • Publisher: 医歯薬出版(株)
• [Book] がん研究の今-1.発がんの分子機構と防御 (笹月健彦、野田哲生編) (2006)
  • Author(s): 畠山 昌則
  • Total Pages: 15
  • Publisher: 東大出版会
• [Book] Recent Advances in Gastrointestinal Carcinogenesis (2006)
  • Author(s): Higashi, H.
  • Total Pages: 13
  • Publisher: TRANSWORLD RESEARCH NETWORK
• [Book] がんのシグナル伝達がわかる(山本雅、仙波憲太郎編, わかる実験医学シリーズ) (2005)
  • Author(s): 大西なおみ, 畠山昌則
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.microbiol.m.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] ヒトK-ras遺伝子転写抑制剤 (2005)
  • Inventor(s): 畠山昌則
  • Industrial Property Rights Holder: 北海道大学
  • Filing Date: 2005-07-01
• [Patent(Industrial Property Rights)] ヒトK-ras遺伝子転写抑制剤 (2005)
  • Inventor(s): 畠山昌則
  • Industrial Property Rights Holder: 北海道大学
  • Filing Date: 2005-07-01
• [Patent(Industrial Property Rights)] ヒトK-ras遺伝子転写抑制剤 (2005)
  • Inventor(s): 畠山昌則
  • Industrial Property Rights Holder: 北海道大学
  • Filing Date: 2005-07-01
• [Patent(Industrial Property Rights)] 国際特許権 (2005)
  • Inventor(s): 畠山 昌則
  • Industrial Property Rights Holder: 北海道大学
  • Filing Date: 2005-07-01