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2000 Fiscal Year Final Research Report Summary

CLONING OF GROWTH FACTORS AND TYROSINE KINASES INVOLVED IN H.pylori-INDUCED GASTRIC CARCINOGENESIS

Research Project

Project/Area Number 11470130
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

CHIBA Tsutomu  KYOTO UNIVERSITY, PROFESSOR, 医学研究科, 教授 (30188487)

Co-Investigator(Kenkyū-buntansha) OKAZAKI Kazuichi  KYOTO UNIVERSITY, ASSOCIATE PROF., 医学研究科, 助教授 (70145126)
Project Period (FY) 1999 – 2000
KeywordsH.pylori / gastric cancer / tyrosine kinase / apoptosis / NF-κB
Research Abstract

Accumulating data suggest involvement of H.pylori infection in the development of gastric cancer. In this study, in order to elucidate roles of H.pylori infection in gastric carcinogenesis, we tried to clone growth factors and tyrosine kinases involved in the development of gastric cancer and adenomas occurred in thymectomised balb/c mice with H.pylori infection, and the following results were obtained ;
(1) Balb/c mice were thymectomised 3 days after birth, and infected with H.pylori at 6-8 weeks. Approximately 50% of the mice developed gastric adenoma in the fundic gland.
(2) At 9 months after infection RNAs were extracted from adenoma and non-adenoma portions of the fundic glands. After construction of single strand cDNAs, subtraction was performed by using mRNAs from non-infected control mice, and cDNA library was made from the remaining cDNAs.
(3) Expression plasmid library was constructed by inserting CMV promotor, transfected to COS cells. Culture medium of the COS cells after 48h incubation was administered to GSMO6 cells, and the plasmid DNA was extracted from the COS cells, the supernatant of which had a significant growth promoting effect on GSMO6 cells. By repeating this procedure, cDNA was finally cloned. We obtained HGF, TGF-α, reg, TNF-α, and IL-1β genes.
(4) cDNA was extracted from the COS cells, the growth ability of which was enhanced, and the cDNA was transfected to GSMO6 cells. After selection, genomes were extracted from the proliferating cells, and the cDNA was sequenced.
(5) From the procedure as mentioned above, genes involved in NF-kB signaling pathway such as NF-kB, traf-6, NIK, and src and cyclin D1 were obtained.
(6) From these data, it is suggested that anti-apoptotic action by various inflammatory cytokines with resulting NF-kB activation is involved in gastric carcinogenesis.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Oshima O,Chiba T, et al.: "Helicobacter-infection in BALB/c mice with post-thymectomy autoimmune gastritis : Induction of follicular gastritis in the corpus."Infect immun. 68. 100-106 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takaishi S,Chiba T, et al.: "Identification of a novel alternative splicing of human FGF receptor 4 : Soluble form splice variant expressed in human gastrointestinal epithelial cells."Biochem Biophys Res Commun. 267. 658-662 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita N.Chiba T, et al.: "The mechanism of transcriptional regulation by methyl-CpG binding protein MBD1."Mol Cell Biol. 20. 5107-5118 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazumori H,Chiba T, et al.: "Neutrophil chemoattractant-2β regulates the expression of the Reg gene in injured gastric mucosa in rats."Gastroenterology. 199. 1610-1622 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Senoh,Chiba T, et al.: "Enhanced expression of transforming growth factor TGF-alpha precursor and TGF-beta 1 during Paneth cell regeneration."Dig Dig Sci. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanai M,Chiba T, et al.: "Blocking of TGF-α-induced ant-apoptotic signaling."Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsushima Y, Kinoshita Y, Watanabe M, Hasan S, Fukui H, Maekawa T, Okada A, Kawanami C, Kishi K, Watanabe N, Nakao M, Chiba T: "Augmentation of water-immersion-stress induced gastric mucosal lesions in BALB/c mice infected with Helicobacter felis."Digestion. 60. 34-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba T: "One more new gastric disease induced by Helicobacter pylori infection, enterochromaffin-like (ECL) cell carcinoid tumor."J Gastroenterol. 34. 545-546 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Date Y, Nakazato M, Yamaguchi H, Kangawa K, Kinoshita Y, Chiba T, Ueta Y, Yamashita H, Matsukura S: "Enterochromaffin-like cells, a cellular source of uroguanylin in rat stomach."Endocrinology. 140. 2398-2404 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba T: "Is reg gene mutation involved in the development of enterochromaffin-like cell carcinoid tumors?"Gastroenterology. 116. 1489-1491 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita N, Takebayashi S, Okumura K, Kudo S, Chiba T, Saya H, Nakao M: "Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein in MBD1 isoforms."Mol Cell Biol. 19. 6415-6426 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida M, Wakatsuki Y, Kobayashi Y, Itoh T, Murakami K, Usui T, Chiba T, Kita T: "Cloning and characterization of a novel membrane- associated antigenic protein of Helicobacter pylori."Infect Immun. 67. 286-293 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda Y, Hijikata M, Takagi S, Chiba T, Simotono K: "New p73 variants with altered C-terminal structure have varied transcriptional activities."Oncogene. 18. 4993-4998 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maekawa T, Waki S, Okada A, Fukui H, Kinoshita Y, Chiba T: "Midkine gene expression in the healing process of gastric ulcer."J Lab Clin Med. 133. 349-352 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe N, Nishitani S, Ikuta K, Chiba T, Honjo T: "Expression levels of B cell surface immunoglobulin regulate efficiency of allelic exclusion and size ofauto-reactive B-1 cell compartment."J Exp Med. 190. 461-469 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh T, Wakatsuki Y, Yoshida M, Usui T, Matsunaga Y, Kaneko S, Chiba T, Kita T: "The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite absence of Helicobacter pylori infection."J Gastroenterol. 34. 560-570 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue F, Chiba T: "Regression of MALT lymphoma of the rectum after anti-H.pylori therapy in a patient negative for H.pylori."Gastroenterology. 117. 514-515 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oshima C, Okazaki K, Matsushima Y, Sawada M, Chiba T, Takahashi K, Hiai H, Katakai T, Kasakura S, Masuda T: "Helicobacter-infection in BALB/c mice with post-thymectomy autoimmune gastritis : Induction of follicular gastritis in the corpus."Infect Immun. 68. 100-106 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takaishi S, Sawada M, Morita Y, Seno H, Fukuzawa H, Chiba T: "Identification of a novel alternative splicing of human FGF receptor 4 : Soluble form splice variant expressed in human gastrointestinal epithelial cells."Biochem Biophys Res Commun. 267. 658-662 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba T, Fukui H, Kinoshita Y: "Reg protein : A possible mediator of gastrin-induced mucosal cell growth."J Gastroenterol. 35. 52-56 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ishihara S, Kaji T, Kawamura A, Rumi MAK, Sato H, Okuyama T, Adachi K, Fukuda R, Watanabe M, Hashimoto T, Hirakawa K, Matsushima Y, Chiba T, Kinoshita Y: "Diagnostic accuracy of a new non-invasive enzyme immunoassay for detecting Helicobacter pylori in stools after eradication therapy."Aliment Pharmacol Ther. 14. 611-614 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita N, Shimotake N, Ohki I, Chiba T, Saya H, Shirakawa M, Nakao M: "The mechanism of transcriptional regulation by methyl-CpG binding protein MBD1."Mol Cell Biol. 20. 5107-5118 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe T, Matsushima Y, Nakase H, Iwano M, Hosotani R, Imamura M, Kinoshita Y, Chiba T: "Effects of Helicobacter pylori infection on Zollinger-Ellison syndrome."J Gastroenterol. 35. 735-741 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe M, Ikuta K, Fagarasan S, Yazumi S, Chiba T, Honjo T: "Migration and differentiation of autoreactive B-1 cells induced by activated γδT cells in antierythrocyte immunoglobulin transgenic mice."J Exp Med. 192. 1577-1586 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kazumori H, Ishihara S, Hoshino E, Kawashima K, Moriyama N, Suetsugu H, Sato H, Adachi K, Fukuda R, Watanabe M, Takasawa S, Okamoto H, Fukui H, Chiba T, Kinoshita Y: "Neurtrophil chemoattractant-2β regulates the expression of the Reg gene in injured gastric mucosa in rats."Gastroenterology. 119. 1610-1622 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazumori H, Ishihara S, Kawashima K, Fukuda R, Chiba T, Kinoshita: "Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection."FEBS Lett. 489. 208-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Seno H, Takaishi S, Sawada M, Chiba T: "Enhanced expression of transforming growth factor TGF-alpha precursor and TGF-beta 1 during Paneth cell regeneration."Dig Dis Sci. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanai M, Nakajima T, Konda Y, Chiba T: "Blocking of TGF-α signaling induces apoptosis of gastric pit cells."Gastroenterology. (in press).

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      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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