ヘリコバクター・ピロリ菌感染を起点とする胃癌発症機構の解析

• Project/Area Number: 15023201
• 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 Univ., Inst for Genetic Med., Prof., 遺伝子病制御研究所, 教授 (40189551)
• Co-Investigator(Kenkyū-buntansha): 東 秀明 北海道大学, 遺伝子病制御研究所, 助教授 (20311227)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥17,200,000 (Direct Cost: ¥17,200,000); Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000); Fiscal Year 2003: ¥8,700,000 (Direct Cost: ¥8,700,000)
• Keywords: Helicobacter pylori / stomach cancer / CagA / SHP-2 / pRBfamily / ESXRI / K-ras / cancer gene therapy / トランスジェニックマウス / Csk / 東アジア型CagA / 西洋型CagA / 遺伝子 / 感染症 / 癌 / 細菌 / シグナル伝達

Research Abstract

(1) Helicobacter pylori CagA and gastric carcinogenesis
Upon translocation into host gastric epithelial cells, H. pylori virulence factor CagA undergoes tyrosine phosphorylation by Src family kinases. We found that the tyrosine-phosphorylated CagA protein specifically binds to SHP-2 or Csk and deregulates the catalytic activity. CagA-activated SHP-2 elicited sustained-activation of Erk MAP kinase and thereby induced cell-morphological transformation, elevated cell motility as well as abnormal cell growth. SHP-2 binds to the EPIYA-containing region of CagA, which shows a significant sequence difference between Western and East Asian CagA species. As a result, East Asian CagA species exhibited stronger SHP-2 binding activity and greater pathological activity than Western CagA species.
(2) Function and regulation of the pRB family tumor suppressor proteins.
We found that the cell cycle-inhibitory activity of the pRB family proteins (pRB, p107 and p130) is collectively regulated by cyclin E a nd cyclin D-dependent phosphorylation. We also found that p107 plays a major role in the growth arrest of cells in S-phase in response to DNA damage. Furthermore, we found that pRB family proteins are capable of transcriptionally inducing cyclin D1 regardless of their phosphorylation status.
(3) Molecular cloning and analysis of ESXR1
We isolated a new human gene, ESXR1, which encodes a paired-like homeoprotein ESXR1. In cells, ESXR1 is proteolytically processed into an N-terminal homeo domain-containing fragment and a C-terminal fragment. The C-terminal fragment localized to the cytoplasm and induced M-phase arrest by inhibiting degradation of M-phase cyclins. On the other hand, the N-terminal fragment localized to the nucleus and acted as a transcriptional repressor. Through genome-wide screening using DNA microarray, we identified the K-ras gene as one of the ESXR1 target genes. Ectopic expression of the ESXR1 N-terminal fragment specifically inhibited growth of human cancer cells that carry gain-of-function mutations in the K-ras gene.

Research Products

• [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
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] EPIYA motif is a membrane targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. (2005)
  • Author(s): Higashi, H.
  • Journal Title: J.Biol.Chem
  • Description: 「研究成果報告書概要(和文)」より
• [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 (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] EPIYA motif is a membrane targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. (2005)
  • Author(s): Higashi, H., Yokoyama, K., Fujii, Y., Ren, S., Yuasa, H., Isaadat, I., Murata-Kamiya, N., Azuma, T., Hatakeyama, M.
  • Journal Title: J.Biol.Chem. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. (2004)
  • Author(s): Azuma, T.
  • Journal Title: J.Infect.Dis 189 Pages: 820-827
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. (2004)
  • Author(s): Zhou, W.
  • Journal Title: FEMS Immunol.Med.Microbiol 40 Pages: 81-87
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Helicobacter pylori CagA provokes Ras-independent morphogenetic response through targeting SHP-2. (2004)
  • Author(s): Higashi, H.
  • Journal Title: J.Biol.Chem. 279 Pages: 17205-17216
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinct diversity of the cag pathogenicity island of Helicobacter pylori in Japan. (2004)
  • Author(s): Azuma, T.
  • Journal Title: J.Clin.Microbiol 42 Pages: 2508-2517
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. (2004)
  • Author(s): Higuchi, M.
  • Journal Title: Cancer Science 95 Pages: 442-447
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Meta-analysis of the relationship between CagA seropositivity and gastric cancer. (2004)
  • Author(s): Azuma, T.
  • Journal Title: Gastroenterology 126 Pages: 1926-1927
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal region that inhibits cyclin degradation. (2004)
  • Author(s): Ozawa, H.
  • Journal Title: Oncogene 23 Pages: 6590-6602
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of human T-cell leukemia virus type-1 (HTLV-1) budding by ubiquitin ligase Nedd4. (2004)
  • Author(s): Sakurai, A.
  • Journal Title: Microbes Infect 6 Pages: 150-156
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oncogenic mechanisms of Helicobacter pylori CagA protein. (2004)
  • Author(s): Hatakeyama, M.
  • Journal Title: Nat.Rev.Cancer 4 Pages: 688-694
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. (2004)
  • Author(s): Azuma, T., Yamazaki, S., Yamakawa, A., Ohtani, M., Muramatsu, A., Suto, H., Ito, Y., Dojo, M., Yamazaki, Y., Kuriyama, M., Keida, Y., Higashi, H., Hatakeyama.M.
  • Journal Title: J.Infect.Dis. 189 Pages: 820-827
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Si, J. and Azuma, T. The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. (2004)
  • Author(s): Zhou, W., Yamazaki, S., Yamakawa, A., Ohtani, M., Ito, Y., Keida, Y., Higashi, H., Hatakeyama.M.
  • Journal Title: FEMS Immunol.Med.Microbiol. 40 Pages: 81-87
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Helicobacter pylori CagA provokes Ras-independent morphogenetic response through targeting SHP-2. (2004)
  • Author(s): Higashi, H., Nakaya, A., Tsutsumi, R., Yokoyama, K., Fujii, Y., Higuchi, M., Takahashi, A., Kurashima, Y., Ishikawa, S., Tanaka, S., Azuma, T., Hatakeyama.M.
  • Journal Title: J.Biol.Chem. 279 Pages: 17205-17216
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinct diversity of the cag pathogenicity island of Helicobacter pylori in Japan. (2004)
  • Author(s): Azuma, T., Yamakawa, A., Yamazaki, S., Ohtani, M., Ito, I/.Muramatsu, A., Suto, H., Yamazaki, Y., Keida, Y., Higashi, H., Hatakeyama, M.
  • Journal Title: J.Clin.Microbiol. 42 Pages: 2508-2517
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. (2004)
  • Author(s): Higuchi, M., Tsutsumi, R., Higashi, H., Hatakeyama, M.
  • Journal Title: Cancer Science 95 Pages: 442-447
  • NAID: 10013723150
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Meta-analysis of the relationship between CagA seropositivity and gastric cancer. (2004)
  • Author(s): Azuma, T., Ohtani M., Yamazaki, Y., Higashi, H., Hatakeyama, M.
  • Journal Title: Gastroenterology 126 Pages: 1926-1927
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal region that inhibits cyclin degradation. (2004)
  • Author(s): Ozawa, H., Ashizawa, S., Naito, M., Yanagihara, M., Ohnishi, N., Maeda, T., Matsuda, Y., Jo, Y., Higashi, H., Kakita, A., Hatakeyama, M.
  • Journal Title: Oncogene 23 Pages: 6590-6602
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] H. Regulation of human T- cell leukemia virus type-1 (HTLV-1) budding by ubiquitin ligase Nedd4. (2004)
  • Author(s): Sakurai, A., Yasuda, J., Takano, H., Tanaka, Y., Hatakeyama, M., Shida
  • Journal Title: Microbes Infect. 6 Pages: 150-156
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. (2004)
  • Author(s): Azuma, T.
  • Journal Title: J.Infect.Dis. 189 Pages: 820-827
• [Journal Article] The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. (2004)
  • Author(s): Zhou, W.
  • Journal Title: FEMS Immunol.Med.Microbiol. 40 Pages: 81-87
• [Journal Article] Distinct diversity of the cag pathogenicity island of Helicobacter pylori in Japan. (2004)
  • Author(s): Azuma, T.
  • Journal Title: J.Clin.Microbiol. 42 Pages: 2508-2517
• [Journal Article] Oncogenic mechanisms of Helicobacter pylori CagA protein. (2004)
  • Author(s): Hatakeyama, M.
  • Journal Title: Nature Rev.Cancer 4 Pages: 688-694
• [Journal Article] Helicobacter pylori causes gastric cancer by hijacking cell growth signaling. (2004)
  • Author(s): Hatakeyama, M.
  • Journal Title: Discovery Medicine 4 Pages: 476-481
• [Journal Article] ヘリコバクター・ピロリ病原因子CagAと胃がん (2004)
  • Author(s): 畠山 昌則
  • Journal Title: 血液・腫瘍科 48 Pages: 235-242
• [Journal Article] ヘリコバクター・ピロリCagAによるSHP-2の脱制御 (2004)
  • Author(s): 東 秀明
  • Journal Title: 細胞工学 23 Pages: 551-555
• [Journal Article] 細胞周期と細胞分化をつなぐRB遺伝子の多面的役割 (2004)
  • Author(s): 手石方 康宏
  • Journal Title: 実験医学 22 Pages: 1808-1813
• [Journal Article] H.pyloriの胃粘膜障害機序-2)宿主側から (2004)
  • Author(s): 堤 良平
  • Journal Title: Surgery Frontier 11 Pages: 24-27
• [Journal Article] Attenuation of Helicobacter pylori CagA-SHP-2 Signaling by Interaction between CagA and C-terminal Src Kinase. (2003)
  • Author(s): Tsutsumi, R.
  • Journal Title: J.Biol.Chem 278 Pages: 3664-3670
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The CagA protein of Helicobacter Pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa. (2003)
  • Author(s): Yamazaki, S.
  • Journal Title: J.Infect.Dis 187 Pages: 334-337
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] NF-_B-dependent induction of cyclin D1 by pRB family proteins and tumor-derived pRB mutants. (2003)
  • Author(s): Takebayashi, T.
  • Journal Title: J.Biol.Chem 278 Pages: 14897-14905
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Helicobacter pylori CagA - a potential bacterial oncoprotein that functionally mimics the mammalian Gab family of adaptor proteins. (2003)
  • Author(s): Hatakeyama, M.
  • Journal Title: Microbes Infect 5 Pages: 143-150
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Helicobacter pylori CagA as a potential bacterial oncoprotein in gastric carcinogenesis. (2003)
  • Author(s): Hatakeyama, M.
  • Journal Title: Pathol.Biol 51 Pages: 393-394
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The Effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells. (2003)
  • Author(s): Azuma T.
  • Journal Title: Aliment.Pharmacol.Ther 18 Pages: 1-6
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. (2003)
  • Author(s): Umehara, S.
  • Journal Title: Oncogene 22 Pages: 8337-8342
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Attenuation of Helicobacter pylori CagA-SHP-2 Signaling by Interaction between CagA and C-terminal Src Kinase. (2003)
  • Author(s): Tsutsumi, R., Higashi, H., Higuchi, M., Okada, M., Hatakeyama, M.
  • Journal Title: J.Biol.Chem. 278 Pages: 3664-3670
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa. (2003)
  • Author(s): Yamazaki, S., Yamakawa, A., Ito, Y., Ohtani, M., Higashi, H., Hatakeyama, M., Azuma, T.
  • Journal Title: J.Infect.Dis. 187 Pages: 334-337
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NF-_B-dependent induction of cyclin D1 by pRB family proteins and tumor-derived pRB mutants. (2003)
  • Author(s): Takebayashi, T., Higashi, H., Sudo, H., Ozawa, H., Suzuki, E., Shirado, O., Katoh, H., Hatakeyama, M.
  • Journal Title: J.Biol.Chem. 278 Pages: 14897-14905
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Helicobacter pylori CagA-a potential bacterial oncoprotein that functionally mimics the mammalian Gab family of adaptor proteins. (2003)
  • Author(s): Hatakeyama, M.
  • Journal Title: Microbes Infect. 5 Pages: 143-150
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Helicobacter pylori CagA as a potential bacterial oncoprotein in gastric carcinogenesis. (2003)
  • Author(s): Hatakeyama, M.
  • Journal Title: (2003) Pathol.Biol. 51 Pages: 393-394
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The Effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells. (2003)
  • Author(s): Azuma T., Yamazaki S, Yamakawa A, Ito Y, Ohtani M, Dojo M, Yamazaki Y, Higashi H, Hatakeyama M.
  • Journal Title: Aliment.Pharmacol.Ther. 18
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. (2003)
  • Author(s): Umehara, S., Higashi, H., Ohnishi, N., Asaka, M., Hatakeyama.M.
  • Journal Title: Oncogene 22 Pages: 8337-8342
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. (2002)
  • Author(s): Higashi, H.
  • Journal Title: Science 295 Pages: 683-686
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. (2002)
  • Author(s): Higashi, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA 99 Pages: 14428-14433
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of pRB-family/E2F complex in the inhibition of IL-3-dependent lymphoid cell proliferation. (2002)
  • Author(s): Yamada, M.
  • Journal Title: Cytokine 17 Pages: 91-97
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Deregulation of SHP-2 tyrosine phosphatase by the Helicobacter pylori virulence factor CagA. (2002)
  • Author(s): Hatakeyama, M.
  • Journal Title: Keio J.Med 51 Pages: 26-32
  • NAID: 130000879575
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. (2002)
  • Author(s): Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., Hatakeyama.M.
  • Journal Title: Science.106747 (2001)Science 295 Pages: 683-686
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. (2002)
  • Author(s): Higashi, H., Tsutsumi, R., Fujita, A., Yamazaki, S., Asaka, M., Azuma, T., Hatakeyama, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA 99 Pages: 14428-14433
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of pRB- family/E2F complex in the inhibition of IL-3-dependent lymphoid cell proliferation. (2002)
  • Author(s): Yamada, M., Kondo, T., Ashizawa, S., Takebayashi, T., Higashi, H., Hatakeyama, M.
  • Journal Title: Cytokine 17 Pages: 91-97
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Deregulation of SHP-2 tyrosine phosphatase by the Helicobacter pylori virulence factor CagA. (2002)
  • Author(s): Hatakeyama. M.
  • Journal Title: Keio J.Med. 51 Pages: 26-32
  • NAID: 130000879575
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Collective Inhibition of pRB Family Proteins by Phosphorylation in Cells with p16^<INK4a> Loss or Cyclin E Overexpression. (2001)
  • Author(s): Ashizawa, S.
  • Journal Title: J.Biol.Chem 276 Pages: 11362-11370
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of pRB-Related p107 Protein in the Inhibition of S-Phase Progression in Response to Genotoxic Stress. (2001)
  • Author(s): Kondo, T.
  • Journal Title: J.Biol.Chem 276 Pages: 17559-17567
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Collective Inhibition of pRB Family Proteins by Phosphorylation in Cells with p16^<INK4a> Loss or Cyclin E Overexpression. (2001)
  • Author(s): Ashizawa, S., Nishizawa, H., Yamada, M., Higashi, H., Kondo, T., Ozawa, H., Kakita, A., Hatakeyama.M.
  • Journal Title: J.Biol.Chem. 276 Pages: 11362-11370
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of pRB-Related p107 Protein in the Inhibition of S-Phase Progression in Response to Genotoxic Stress. (2001)
  • Author(s): Kondo, T., Higashi, H., Nishizawa, H., Ishikawa, S., Ashizawa, S., Yamada, M., Makita, Z., Koike, T., Hatakeyama.M.
  • Journal Title: J.Biol.Chem. 276 Pages: 17559-17567
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and Characterization of Elongin A2, a new member of the elongin family of transcription elongation factors, specifically expressed in the testis. (2000)
  • Author(s): Aso, T.
  • Journal Title: J.Biol.Chem 275 Pages: 6546-6552
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] β3-endonexin as a novel inhibitor of cyclin A-associated kinase. (2000)
  • Author(s): Ohtoshi, A.
  • Journal Title: Biochem.Biophys.Res.Comm 267 Pages: 947-952
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Human p55^<CDC>/Cdc20 associates with cyclin A and is phosphorylated by cyclin A-Cdk2 complex. (2000)
  • Author(s): Ohtoshi, A.
  • Journal Title: Biochem.Biophys.Res.Comm 268 Pages: 530-534
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ras and STAT are essential and sufficient downstream components of JAKs in cell proliferation. (2000)
  • Author(s): Mizuguchi, R.
  • Journal Title: Jpn.J.Cancer Res 93 Pages: 527-533
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and Characterization of Elongin A2, a new member of the elongin family of transcription elongation factors, specifically expressed in the testis. (2000)
  • Author(s): Aso, T., Yamazaki, K., Amimoto, K., Kuroiwa, A., Higashi, H., Matsuda, Y., Kitajima, S., Hatakeyama.M.
  • Journal Title: J.Biol.Chem. 275 Pages: 6546-6552
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] β3-endonexin as a novel inhibitor of cyclin A-associated kinase. (2000)
  • Author(s): Ohtoshi, A., Maeda, T., Higashi, H., Ashizawa, S., Yamada, M., Hatakeyama.M.
  • Journal Title: Biochem.Biophys.Res.Comm. 267 Pages: 947-952
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Human p55^<CDC>/Cdc20 associates with cyclin A and is phosphorylated by cyclin A-Cdk2 complex. (2000)
  • Author(s): Ohtoshi, A., Maeda, T., Higashi, H., Ashizawa, S., Yamada, M., Hatakeyama, M.
  • Journal Title: Biochem.Biophys.Res.Comm. 268 Pages: 530-534
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ras and STAT are essential and sufficient downstream components of JAKs in cell proliferation. (2000)
  • Author(s): Mizuguchi, R., Noto, S., Yamada, M., Ashizawa, S., Higashi, H., Hatakeyama.M.
  • Journal Title: Jpn.J.Cancer Res. 93 Pages: 527-533
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 細胞工学 23 (2004)
  • Author(s): 東 秀明
  • Total Pages: 4
  • Publisher: ヘリコバクター・ピロリCagAによるSHP-2の脱制御
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 実験医学 22 (2004)
  • Author(s): 手石方 康宏
  • Total Pages: 5
  • Publisher: 細胞周期と細胞分化をつなぐRB遺伝子の多面的役割
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 腫瘍学総論 病態病理学(分担)(菊池浩吉監修) (2004)
  • Author(s): 畠山 昌則
  • Publisher: 南山堂
• [Book] 実験医学(増刊)21 (2003)
  • Author(s): 畠山 昌則
  • Total Pages: 5
  • Publisher: 細菌由来タンパク質による細胞内シグナル伝達系の撹乱と発癌
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 実験医学 20 (2002)
  • Author(s): 畠山 昌則
  • Total Pages: 4
  • Publisher: ヘリコバクター・ピロリ菌感染を起点とする胃発癌分子機構-胃癌研究の最前線
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Molecular Medicine 38 (2001)
  • Author(s): 畠山 昌則
  • Total Pages: 3
  • Publisher: 癌とサイトカイン、増殖因子/オートクリン、パラクリン機構
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] 特許権 (2004)
  • Inventor(s): 畠山 昌則
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 2004-315291
  • Filing Date: 2004-10-29
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsutsumi, R.: "Attenuation of helicobacter pylori CagA-SHP-2 signaling by Interaction between CagA and C-terminal Src kinase."J.Biol.Chem.. 278. 3664-3670 (2003)
• [Publications] Yamazaki, S.: "The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa."J.Infect.Dis.. 187. 334-337 (2003)
• [Publications] Takebayashi, T.: "NF-kB-dependent induction of cyclin D1 by pRB family proteins and tumor-derived pRB mutants."J.Biol.Chem.. 278. 14897-14905 (2003)
• [Publications] Umehara, S.: "The effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma."Oncogene. 13. 8337-8342 (2003)
• [Publications] Hatakeyama, M.: "Helicobacter pylori CagA - a potential bacterial oncoprotein that functionally mimics the mammalian Gab family of adaptor proteins."Microbes Infect. 5. 143-150 (2003)
• [Publications] Hatakeyama, M.: "Helicobacter pylori CagA as a potential bacterial oncoprotein in gastric carcinogenesis."Pathol.Biol.. 51. 393-394 (2003)
• [Publications] Azuma, T.: "The effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells."Aliment.Pharmacol.Ther.. 18. 1-6 (2003)
• [Publications] Zhou, W.: "The diversity of vacA and cagA genes of Helicobacter pylori in East Asia."FEMS Immunol.Med.Microbiol.. 40. 81-87 (2004)
• [Publications] Azuma, T.: "Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer."J.Infect.Dis.. 189. 820-827 (2004)
• [Publications] Sakurai, A.: "Regulation of human T-cell leukemia virus type-I budding by ubiquitin ligase Nedd4."Microbes Infect. (In press).
• [Publications] Higashi, H.: "Helicobacter pylori CagA provokes Ras-independent morphogenetic response through targeting SHP-2."J.Biol.Chem.. (In press).