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1998 Fiscal Year Final Research Report Summary

ALTERED GROWTH CONTROL OF HEPATOCYTES DURING THE CARCINOGENESIS AND ITS REGULATION

Research Project

Project/Area Number 09470138
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

KAWATA Sumio  Osaka University Medical School, Associate Professor, 医学部, 助教授 (90183285)

Co-Investigator(Kenkyū-buntansha) KISO Shinichi  Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
FUKUDA Kazuto  Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
TAMURA Shinji  Osaka University Medical School, Assistant Professor, 医学部, 助手 (30243223)
Project Period (FY) 1997 – 1998
KeywordsHepatocellular carcinoma / TGF-b / TGF-b receptor / gene mutation / cell growth
Research Abstract

We are studying on altered control on hepatocytes growth during the carcinogensis. The altered regulation seems to be derived from escape from negative growth control by TGF-b via , a loss of responsivity of hepatocytes. Our hypothesis is that ther is not only defect of TGF-b receptor but also alteration of the signal transduction pathway of the cytokine.
To determined wether Src kinase is involved in TGF-b signaling, we examined the effects of TGF-b1 on Src in rat fibroblast- cell line 3Y1 and in v-Src-transformed 3Y1 (SR-3Y1). TGF-b1 inhibited MAP kinase activity and inhibited growth in SR-3Y1 cells, while it did not affect the growth of 3Y1 cells. TGF-b1 significantly decreased v-Src kinase activity and protein abundance in SR-3Y1 cells, mainly by accelerating the degradation of v-Src. In contrast, in 3Y1 cells, TGF-b1 did not affect c-Src abandance or kinase activity. however, upon activation of c-Src in 3Y1 cells by PDGF, TGF-b1 decreased Src abundance. Additionally, in 3Y1 cells transfected with an activated c-Src mutant which lacks the SH3 domain, its level was decreased by TGF-b1 treatment. These findings suggest that TGf-b1 specifically induces degradation of activated Src kinase. This may be a novel mechanism for cross-talk between growth factors and TGF-b.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] K.Fukuda,S.Kawata,et al.: "Transforming growth factor-β induced degradation of activated Src tyrosine kinase in rat fibroblasts." Oncogene. 16. 3349-3356 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Fukuda,S.Kawata,et al.: "Altered regulation of Src tyrosine kinase by transforming growth factor-β in a human hepatoma cell line." Hepatology. 28. 796-804 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Tsushima,S.kawata,et al.: "Reduced plasma TGF-β1 levels in patients with chronic hepatitis C after interferon-α." J.Hepatol.30. 1-7 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Imai,S.kawata,et al.: "Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C." Ann.Intern.Med.129. 94-99 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Nagase,S.kawata,et al.: "Effect of farnesyltransferase overexpression on cell growth and transformation." Int.J.Cancer. 80. 126-133 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Nagase,S.Kawata,et al.: "Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth." Brit.J.Cancer. 76. 1001-1010 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河田純男: "肝臓病学。ヒト肝癌と細胞増殖因子。" 医学書院, 904 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田村信司,河田純男: "がんの浸潤・転移。TGF-βとがんの発育,進展" 医学書院, 329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Fukuda, S.Kawata, et al.: "Transforming growth factor-b induced degradation of activated Src tyrosine kinase in rat fibroblasts." Oncogene. 16. 3349-3356 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Fukuda, S.Kawata, et al.: "Altered regulation of Src tyrosine kinase by transforming growth factor-b in a human hepatoma cell line." Hepatology. 28. 796-804 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Tsushima, S.Kawata, et al.: "Reduced plasma TGF-bl levels in patients with chronic hepatitis C after interferon-alpha." J.Hepatol. 30. 1-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Imai, S.Kawata, et al.: "Effect of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C." Ann.Inern.Med.129. 94-99 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Nagase, S.Kawata, et al.: "Effect of farnesy1-transferase overexpression on cell growth and transformation." Int.J.cancer. 80. 126-133 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Nagase, S.Kawata, et al.: "Manumycin and gliotoxin derivatives KT7595 block Ras farnesylation and cell growth." Brit.J.Cancer. 76. 1001-1010 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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