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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 02151040
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) 高久 史麿  国立病院医療センター, 院長 (40048955)
津田 均  国立がんセンター研究所, 病理部, 研究員 (70217321)
河野 通明  岐阜薬科大学, 助教授 (00027335)
春日 雅人  神戸大学, 医学部, 教授 (50161047)
清水 信義  慶応大学, 医学部, 教授 (50162706)
Project Period (FY) 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 1990: ¥12,500,000 (Direct Cost: ¥12,500,000)
Keywords増殖因子 / TGFβ / レセプタ-系 / EGFレセプタ- / TGFα / 増殖因子系遺伝子の転写因子 / 癌遺伝子 / チロシンキナ-ゼ
Research Abstract

1.6種の胃癌細胞株を用いてのTGFβのシグナル伝達系の解析により、TGFβI型受容体からの増殖抑制シグナル系と、TGFβII、III型受容体からPKC、CREBを介してのもう一つの異なるシグナル系の存在が考えられた。又、EGFRをもつヒト肺腺癌細胞(A549)を用いて、EGF、TGFβ、TPAが誘導するEGFR遺伝子の発現促進について解析した結果、TGFβは、EGF、TPAとは異なるシグナル伝達系を介してEGFR遺伝子の転写を制御する可能性が示唆された。又、TGFβのリコンビナント体を大量に作成することに成功し、現在これによりTGFβ受容体の精製が進んでいる(田原、清水、高久)。2.EGFR欠損肺小細胞癌から分離された形態変異株及び胃癌細胞株におけるEGFR遺伝子発現の調節を見ると、負の転写因子であるGCFがEGFR遺伝子の転写制御に重要な役割を演じており、更に、GCF遺伝子導入胃癌細胞を用いての研究成果から、GCFは、EGFRのみならずTGFα遺伝子の発現にも抑制的に働く可能性が示唆された(田原、清水)。3.cーRaf蛋白の受容体型チロシンキナ-ゼを介するシグナル伝達機構の解明のため、インスリン受容体cDNA、cーRaf cDNA導入NIH3T3細胞を用いてcーRaf蛋白の燐酸化を検討した結果、cーRaf蛋白は受容体チロシンキナ-ゼの直接の基質とはならず、燐酸化のカスケ-ドのより下流に位置し、他のキナ-ゼによりセリン・スレオニン燐酸化をうけてその活性化がおきると考えられた。4.TGFβを除く、正の増殖因子、EGF、FGF、PDGFなどの増殖因子のシグナル伝達系における一つの共通な中継反応として、細胞質41K、43K蛋白のチロシン燐酸化反応が同定された(河野)。5.INTー2遺伝子の増幅がヒト肝癌の悪性度と相関し、ERBB2遺伝子の増幅は原発巣より転移巣(40%)に頻発し、しかも癌遺伝子コピ-数も転移巣で高いことが示された(津田)。

Report

(1 results)
  • 1990 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Yoshida,K.,Kyo,E.,Tsuda,T.,Tsujino,T.,Ito,M.,Niimoto,M.and Tahara,E.: "EGF and TGFーα,the ligands of hyperproduced EGFR in human esophageal carcinoma cells,act as autocrine growth factors" Int.J.Cancer. 45. 131-135 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoshida,K.,Kyo,E.,Tsujino,T.,Sano,T.,Niimoto,M.and Tahara,E.: "Expression of epidermal growth factor,transforming growth factorーα and their receptor genes in human gastric carcinomas;Implication for autocrine growth" Jpn.J.Cancer Res.81. 43-51 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Oda,N.,Tsujino,T.,Tsuda,T.,Yoshida,K.,Nakayama,H.,Yasui,W.,and Tahara,E.: "DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas" Virchows Archiv B Cell Pathol. 58. 273-277 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tahara,E.: "Growth factors and oncogenes in human gastrointestinal carcinomas" J Cancer Res Clin Oncol. 116. 121-131 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsujino,T.,Yoshida,K.,Nakayama,H.,Ito,H.,Shimosato,T.and Tahara,E.: "Alterations of oncogenes in metastatic tumours of human gastric carcinomas" Br.J.Cancer. 62. 226-230 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takekura,N.,Yasui,W.,Yoshida,K.,Tsujino,T.,Ito,H.,Tahara,E.,et al.: "pp60^<cーsrc> protein kinase activity in human gastric carcinomas" Int.J.Cancer. 45. 847-851 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoshida,K.,Tsujino,T.,Yasui,W.,Kameda,T.,Sano,T.,Tahara,E.,et al.: "Induction of growth factorーreceptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factorーα in human gastric carcinoma cell line MKNー28" Jpn.J.Cancer Res.81. 793-798 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoshida,K.,Yasui,W.,Ito,H.,and Tahara,E.: "Growth factors in progression of human esophageal and gastric carcinomas" Exp.Pathol.40. 291-300 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kameda,T.,Yasui,W.,Yoshida,K.,Tsujino,T.,Nakayama,H.,Ito,M.,Tahara,E.,et al.: "Expression of ERBB2 in human gastric carcinomas:Relationship between pl85^<ERBB2> expression and the gene amplification" Cancer Research. 50. 8002-8009 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kajikawa,K.,Yasui,W.,Sumiyoshi,H.,Yoshida,K.,Nakayama,H.,Tahara,E.,et al.: "Expression of epidermal growth factor in human tissues" Virchows Archiv A Pathol Anat. 418. 27-32 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Gamou,S.,Shimosato,Y.and Shimizu,N.: "Regulation of the epidermal growth factor (EGF) receptor gene expression in a morphological variant isolated from an EGF receptorーdeficient SCLC cell line" Cell Growth & Differentiation. 1(8). 351-359 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirai,M.and Shimizu,N.: "Purification of two distinct proteins of apporoximate Mr 80,000 from human epidermal cells and identification as proper substrates for protein kinase C" Biochem.J.270(3). 583-589 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hirai,M.,Kobayashi,M.and Shimizu,N.: "Reduced tyrosine phosphorylation and nonresponsiveness to EGFーmediated cytotoxity in EGF a receptorーhyperproducing UCVAー1 cells" Cell.Signal.2(3). 245-252 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hori,T.,Yamanaka,Y.,Hayakawa,M.,Shibamoto,S.,Oku,N.and Ito,F.: "Growth inhibition of human fibroblasts by epidermal growth factor in the presence of arachidonic acid" Biochem.Biophys.Res.Commun.169. 959-965 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shibamoto,S.,Hori,T.,Hayakawa,M.,Nango,M.,Cragoe,E.,Oku,N.and Ito,F.: "Inhibitory effect of local anesthetics on Na^+/H^+ antiporter in brush border membranceーreconstituted vesicles" Life Science. 47. 1129-1133 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hori,T.,Yamanaka,Y.,Hayakawa,M.,Shibamoto,S.,Oku,N.,Ito,F.et al.: "Prostaglandins antagonize fibroblast proliferation stimulated by tumor necrosis factor" Biochem.Biophys.Res.Commun.174. 758-766 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shiba,T.,Tobe,K.,Koshio,O.,Yamamoto,R.,Shibasaki,Y.,Kasuga,M.et al.: "Concanavalin Aーinduced receptor aggregation stimulates the tyrosine kinase activity of the insulin receptor in intact cells" Biochem.J.267. 787-794 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamanoto,R.,Koshio,O.,Tobe,K.,Shibasaki,Y.,Kasuga,M.,et al.: "Phosphorylation state and biological function of a mutant human insulin receptor Val^<996>" J.Biol.Chem.265. 14777-14783 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Izumi,T.,Tamemoto,H.,Nagao,M.,Kadowaki,T.,Takaku,F.and Kasuga,M.: "Insulin and plateletーderived growth factor stimulate phosphorylation of the Cーraf product at serine and threonine residues in intact cells" J.Biol.Chem.

    • Related Report
      1990 Annual Research Report
  • [Publications] Kohno,M.,Nishizawa,N.,Tsujimoto,M.,and Nomoto,H.: "Mitogenic signaling pathway of tumour necrosis factor involves the rapid tyrosine phosphrylation of 41000ーMr and cytosol proteins" Biochem.J.267. 91-98 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Zu,Y.,Kohno,M.,Kubota,I.,Nishida,E.,Hanaoka,M.,Namba,Y.: "Characterization of interleukin 2 stimulated 65ーkilodalton phosphoprotein in human T cells" Biochemistry. 29. 1055-1062 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Zu,Y.,Shigesada,K.,Nishida,E.,Kubota,I.,Kohno,M.,Hanaoka,M.,Namba,Y.: "65ーkilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actinーbinding sites and two calciumーbinding sites" Biochemistry. 29. 8319-8324 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nishizawa,N.,Okano,Y.,Chatani,Y.,Amamoto,F.,Tanaka,E.,Kohno,M.et al.: "Mitogenic signaling pathways of growth factors can be distuinguished by the involvement of pertussis toxinーsensitive guanosine triphosphateーbinding protein and of protein kinase C" Cell Regulation. 1. 747-761 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takasuka,T.,NinomiyaーTsuji,J.,Sakayama,M.,Ide,T.et al.: "Atemperatureーsensitive cellーcycle mutant ofmammalian cells,tsJT 16,is defective in a function operation soon after growth stimulation" Cell Structure and Function. 15. 39-45 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takasuka,T.,Sakayama,M.,Ishibashi,S.,and Ide,T.: "tsJT16,a cellーcycle ts mutant defective in a function operating soon after growth stimulation,fails to induce a primarily activated labile nuclear protein" Cell Structure and Function. 15. 47-52 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakahara,M.,Fukushima,M.,Tacho,T.,Usui,T.,and Ide,T.: "Establishment of a SV40ーtransformed cell line from primary culture of rat dors olateral prostatic epithelial cells" Experimental Cell Research. 190. 271-275 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tai,Y.,NinomiyaーTsuji,J.,Furuoku,K.,Ogawa,N.,Ide,T.,et al.: "Nonーlethal GOーts mutant tsJT60 becomes lethal at the nonpermissive temperature after transformation:Ahint for new cancer chemotheraーpeutics" Cell Structure and Function. 15. 385-391 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takasuka,T.,Sakayama,M.,Miyake,E.,Ishibashi,S.,and Ide,T.: "A nuclear labile protein,p70,was expressed exclusively during GOーS transition but not in Gl phase of a cell cycle ts mutant,tsJT16" Cell Structure and Function. 16. 81-85 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuyama,N.,Miura,M.,Kitahira,M.,Ishibashi,S.,and Ide,T.: "SV40 Tーantigen is required for maintainance of immortal growth in SV40ーtransformed human fibroblasts" Cell Structure and Function. 16. 55-62 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuji,K.,Ueno,A.,and Ide,T.: "Dual effects of protein kinase C on the induction of DNA synthesis by colcemid in GOーarrested human diploid fibroblasts" Cell Structure and Function. 16. 73-80 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuda,H.,Zhang,W.,Shimosato,Y.,Yokota,J.,Terada,M.,Sugimura,T.,et al.: "Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma" Proc.Natl.Acad.Sci.USA. 87. 6791-6794 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuda,H.,Hirohashi,S.,Shimosato,Y.,Hirota,T.,Tsugane,S.,et al.: "Correlation between histologic grade of malignancy and copy number of cー<erb>___ーBー2 gene in breast carcinoma" Cancer. 65. 1794-1800 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuda,H.,Hirohashi,S.,Hirota,T.,and Shimosato,Y.: "Alterations in copy number of cー<erb>___ーBー2 and cー<myc>___ー protoーoncogenes in advanced stage of human breast cancer" Acta.Pathol.Jpn.41. 19-23 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hattori,Y.,Kato,O.,et al.: "Kーsam,an amplified gene in stomach cancer,is a member of the heparinーbinding growth factor receptor genes" Proc.Natl.Acad.Sci.USA. 87. 5983-5987 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 加藤 修、他: "ヒトーマウス融合トランスフォ-ミング遺伝子<fum>___ーを構成するマウス<hst2>___ー遺伝子" 第49回日本癌学会総会記事抄録集. 163. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 飯田 信也、加藤 修、他: "<hstー2>___ー遺伝子cDNAの解析" 第13回日本分子生物学会年会講演要旨集. 196. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Piao,YーF.,Ichijo,H.,Miyagawa,K.,Ohashi,H.,Takaku,F.,and Miyazono,K.: "Latent form of transforming growth factorーβ1 acts as a potent growth inhibitor on a human erythroleukemia cell line" Biochem.Biophys.Res.Commun.167. 27-32 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tsuruo,T.,Naito,M.,Takamori,R.,Tsukahara,S.,Yamagishi,T.,et al.: "A benzophenazine derivative,Nーβーdimethylaminoethyl 9ーcarboxyー5ーhydroxyー10ーmethoxyーbenzo[a]phenazineー6ーcarboxamide,as a new antitumor agent against multidrugーresistant and sensitive tumors" Cancer Chemother.Pharmacol.26. 83-87 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sato,W.,Yusa,K.,Naito,M.,and Tsuruo,T.: "Staurosporine,a potent inhibitor of cーkinase,enhances drug accumulation in multidrugーresistant cells" Biochem.Biopys.Res.Commun.173. 1252-1257 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Watanabe,M.,Komeshima,N.,Naito,M.,Tsuruo,T.,et al.: "Cellular pharmacology of MX2,a new morpholino anthracycline,in human pleiotropic drugーresistant cells" Cancer Research. 51. 157-161 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kato,M.,and Takenawa,T.: "Purification and characterization of membraneーbound and cytosolic forms of diacylglycerol kinase from rat brain" J.Biol.Chem.265. 794-800 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yuasa,Y.,Kamiyama,T.,Kato,M.,Iwama,T.,Tonomura,A.,et al.: "Transforming genes from familial adenomatous polyposis patient cells detected by a tumorigenicity assay" Oncogene. 5. 589-596 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takenawa,T.,Kato,M.,and Yamakawa,A.: "Second Messenger and Phosphoprotein Research" Ed.by Nishizuka,Y.,Raven Press, 317-322(5) (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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