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癌の増殖における増殖因子の相互作用とその分子機構

Research Project

Project/Area Number 03151043
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionHiroshima University

Principal Investigator

田原 榮一  広島大学, 医学部, 教授 (00033986)

Co-Investigator(Kenkyū-buntansha) 豊島 秀男  東京大学, 医学部, 助手 (20197966)
河野 通明  岐阜薬科大学, 薬学部, 助教授 (00027335)
伊藤 文昭  摂南大学, 薬学部, 教授 (80111764)
春日 雅人  神戸大学, 医学部, 教授 (50161047)
清水 信義  慶應義塾大学, 医学部, 教授 (50162706)
Project Period (FY) 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥18,800,000 (Direct Cost: ¥18,800,000)
Fiscal Year 1991: ¥18,800,000 (Direct Cost: ¥18,800,000)
Keywords増殖因子 / GCF / 転写因子 / FGF / cーmet / cripto / PDーECGF / インスリン受容体 / チロシンキナ-ゼ
Research Abstract

GCF(GC rich配列結合蛋白)は、異なった複数の増殖因子・受容体(TGFα,EGF受容体,ERBB2,FGF受容体ー1)遺伝子プロモ-タ-に結合し、それらの遺伝子発現を抑制する負の共通した転写因子であることが実証され、更に、GCF遺伝子導入胃癌細胞株では、TGFα・ERF受容体の減少とともに、癌細胞自己増殖の著しい減少がin vitro,in vivoで確認された(田原)。次に、ヒト肝細胞増殖因子(HGF)遺伝子は染色体7q21.1に位置すること(清水)、また同じ7qに存在するHGF受容受体遺伝子cーmetの異常(欠失、増幅)は胃癌に頻発すること、cーmet mRNA 6.0kb transcriptは胃癌細胞のみに発現して、その進展・転移とよく相関することなどか明らかにされた(田原)。又、HGFによって胃癌細胞株の増殖促進、cーmet蛋白の自己リン酸化、プログタグランジン産生などが惹起され(田原、伊藤)、更に種々のペプチド増殖因子によって誘導される細胞質41k,43k蛋白質チロシンリン酸化をもHGFによって起きることが示された(河野)。新しいEGF関連遺伝子、criptoの臓器別発現では、甲状腺、腸、腎に高く、腫瘍では大腸癌、高分化胃癌に特徴的に高い発現を示し、その進展と相関することが明らかにされた。又、血小板由来血管内皮細胞増殖因子(PDーECGF)は、ヒト肝実質細胞と肝細胞癌に特異的に発現しており、肝実質細胞の自己増殖因子である可能性が示唆された(豊島)。インスリン受容体を介するシグナル伝達系に関しては、siteーdirected mutagenesisの手法を用いて、各種の変異受容体を作製してその機能を検討した結果、インスリン受容体のレベルで各種インスリン作用が分岐している可能性が示され(春日)、更にヒトKB細胞ではインスリンがEGF依存性増殖を抑制し、一方、TGFβ1もEGF依存性増殖を阻害するが、インスリン依存性増殖には大きな影響を及ぼさないことが明らかにされた(天野)。

Report

(1 results)
  • 1991 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Kuniyasu H: "Expression of cripto,a novel gene of the epidermal growth factor family,in human gastrointestinal carcinomas." Japanese Journal of Cancer Research. 82. 969-973 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanimoto H: "Expression of basic fibroblast growth factor in human gastric carcinomas." Virchows Archiv B Cell Pathol. 61. 263-267 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kajikawa K: "Expression of epidermal growth factor in human tissues.Immunohistochemical and biochemical analysis." Virchows Archiv A Pathol Anat. 418. 27-32 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ito M: "Growth inhibition of transforming growth factor β on human gastric carcinoma cells:Receptor and postreceptor signaling." Cancer Research. 52. 295-300 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ito M: "Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas." Japanese Journal of Cancer Research. 83. 86-92 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukuyama R: "Flow cytometric analysis of the expression of 9A3 antigen,E-cadherin and EGF receptor in TMK-1 stomach cancer cells." Int.J.Cancer. 48. 81-84 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Iida S: "Human hst-2(FGF-6) oncogene:cDNA cloning and characterization." Oncogene.

    • Related Report
      1991 Annual Research Report
  • [Publications] Toyoshima H: "Identification of platelet-derived endothelial cell growth factor as an potential autocrine growth regulator of the hepatocytes."

    • Related Report
      1991 Annual Research Report
  • [Publications] Amano F: "A lipopolysaccharide (LPS)-resistant mutant isolated from a macrophage-like cell line,J774.1,exhibits an altered activated-macrophage phenotype in response to LPS." Infect.Immun.59. 2166-2174 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Amano F: "Isolation and characterization of a mutant cel line defective in maturation and processing of EGF receptors from KB mutant cells resistant of EGF-Pseudomonas exotoxin conjugates."

    • Related Report
      1991 Annual Research Report
  • [Publications] Sasaki A: "Application of lectin and B-lympho-cytes-specific monoclonal antibodies for the demonstration of human microglia in formalin-fixed,paraffin-embedded brain tissue." Virchows Archiv A Pathol Anat.419. 291-299 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Moses H: "Identification of an interferon-γ-responsive element of a class II major histocompatibility gene in rat type 1 astrocytes." J.Neuroimmunol.35. 273-278 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yokoi T: "Atypical mesothelial hyperplasia associated with bronchogenic carcinoma." Human Pathology. 22. 695-699 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Eugene J.Mark: "Absence of evidence for a significant background incidence of diffuse malignant mesothelioma,apart from asbestos exposure." Ann New York Acad Sci.

    • Related Report
      1991 Annual Research Report
  • [Publications] Nakayama A: "Immunocytochemical observation of paraquat-Induced alveolitis:with special reference to class II MHC antigens." Virchows Arch B.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kasayama S: "Heparin inhibits autocrine stimulation but not fibroblast growth factor stimulation of cell proliferation of androgen-responsive Shionogi carcinoma." J.Cell Physiol.148. 260-266 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sumitani S: "Effects of thyroid hormones on androgen-or basic fibroblast growth factor(bFGF)-induced proliferation of Shionogi carcinoma 115 mouse mammary carcionoma cells in serum-free culture." Cancer Research. 51. 4323-4327 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Saito H: "Up-regulation of fibroblast growth factor (FGF) receptor mRNA levels by basic FGF or testosterone in androgen-sensitive mouse mammary tumor cells." Biochem.Biophys.Res.Commun.174. 136-141 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Motozaki T: "Cholecystokinin inhibits phosphatidylcholine synthesis via CA^<2+>-calmodulin-dependent pathway in isolated rat pancreatic acinti:A possible mechanism for diacylgycerol accumulation." J.Biol.Chem.(1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tobe K: "Insulin and 12-o-tetradecanoyl phorbol 13-acetate (TPA) activation of two immunologically distinct MBP/MAP2 kinases via de novo phosphorylation of threonine and tyrosine residues." J.Biol.Chem.(1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsuji K: "Dual effect of protein kinase C on the induction of DNA synthesis by colcemid in GO-arrested human diploid fibroblasts." Cell Struct.Funct.16. 73-80 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsuyama N: "SV40 T-antigen is required for maintainance of immortal growth in SV40-transformed human fibroblasts." Cell Struct.Funct.16. 55-62 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miyake E: "A cell cycle ts mutant,tsJT16,is defective in p70 synthesis through protein kinase C-dependent and -independent pathways." Cell Struct.Funct.16. 315-321 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kihana T: "Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation." Jpn.J.Cancer Res.82. 308-314 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukuyama R: "Detection of EGF receptors and E-cadherins in the basolateral membrane of A431 cells by laser scanning fluorescence microscopy." Japanese Journal of Cancer Research. 82. 8-11 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukuyama R: "Expression of epidermal growth factor (EGF) and EGF receptor in human tissues." J.Exp.Zool.258. 336-343 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukuyama R: "Regional localization of the hepatocyte growth factor (HGF) gene to human chromosome 7 band q21.1." Genomics. 11. 410-415 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hori T: "Prostaglandins antagonize fibroblast proliferation stimulated by tumor necrosis factor." Biochem.Biophys.Acta.174. 758-766 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hayakawa M: "Solubilization of human placental tumor necrosis factor receptors as a complex with a guanine nucleotide-binding protein." Arch.Biochem.Biophys.286. 323-329 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hayakawa M: "Involvement of prostaglandin-producing pathway in the cytotoxic action of tumor necrosis factor." Cell Struc.Funct.16. 333-340 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kouhara H: "Expression cDNA cloning of fibroblast growth factor (FGF) receptor in mouse breast cancer cells." Biochem.Biophys.Res.Commun.176. 31-37 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akatsuka A: "Electoron microscopic identification of the intracellular secretion pathway of human G-CSF in a human tumor cell line:A comparative study with a chinese hamster ovary cell line (IAI-7) transfected with human G-CSF cDNA." Experimental Hematology. 19. 768-772 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sato M: "Control Cell Growth and Gene Expression." Japan Sci.Soc.Press Tokyo/Springer-Verlag,Berlin, 20 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 田原 榮一: "現代病理学大系17B" 中山書店, 40 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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