• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The role of DPC4 and Smad family genes iu the carcinogenesis of the digestive system.

Research Project

Project/Area Number 09670590
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

KAWABATA Masahiro  The Cancer Institute, Biochemistry Associate Member, 癌研究所・生化学部, 主任研究員 (60224838)

Co-Investigator(Kenkyū-buntansha) HANAI Jun-ichi  The Cancer Institute, Biochemistry Associate, 癌研究所・生化学部, 研究員 (70261964)
KATO Mitsuyasu  The Cancer Institute, Biochemistry Associate, 癌研究所・生化学部, 研究員 (20194855)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsTGF-beta / DPC4 / Smad / colorectal cancer / Drosophila
Research Abstract

(1) We identified novel Drosophila Smads, Medea and dSmad2.We proved, through the biochemical characterization of these Smads, that the signaling pathway by Smads is conserved between Drosophila and mammals.
(2) Smad2 and Smad3 exist as monomers m the absence of TGF-beta stimulation, and form homo- and hetero-oligomers with Smad4 upon phosphorylation by TGF-beta receptor.Both homomeric and hetero-meric Smad3 were capable to bind to DNA.
(3) A mutation of Smad2 found in colorectal cancers was introduced to the corresponding position in Smad3.The mutant Smad3 interfered with the phosphorylation of the wild type Smad2 and Smad3, thereby inhibiting the transactivation and growth inhibition of HaCat cells by TGF-beta.Thus the mutation not only disrupts the normal function of Smads, but is likely to positively contributes to the car-cinogenesis in a dominant-negative fashion.
(4) We identified a germline mutation of the TGF-beta type II receptor gene in RER-negative hereditary non-polyposis colorectal cancer (HNPCC), which generalizes that TGF-beta suppresses the colorectal carcinogenesis.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Imamura T.,Takase,M.,Miyazono,K.,et al.: "Smad6 inhibits signalling by the TGF-β superfamily." Nature. 389・6651. 622-626 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakao,A.,Afakhte,M.,Moren,A.,et al.: "Identification of Smad7,a TGF-β inducible antagonist of TGF-β signalling." Nature. 389・6651. 631-635 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakao,A.,Imamura,T.,Miyazono,K.,et al.: "TGF-β receptor-mediated signalling through Smad2, Smad3 and Smad4." EMBO.Journal. 16・17. 5353-5362 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Beppu,H.,Kawabata,M.,Miyazono,K.,et al.: "cDNA cloning and genomic organization of the mouse BMP type II receptor." Biochem.Biophys.Res.Commum.235・3. 499-504 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu,A.,Kato,M.,Miyazono,K.,et al.: "Identification of receptors and Smad proteins involved in activin signaling in a human epidermal keratinocyte cell line." Genes to Cells. 3・2. 125-134 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takase,M.,Imamura,T.,Miyazono,K.,et al.: "Induction of Smad6 mRAN by bone morphogenetic proteins." Biochem.Biophys.Res.Commum.244・1. 26-29 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagisawa,J.,et al.: "Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators." Science. 印刷中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishihara,A.,et al.: "Role of p300,a transcriptional coactivator,in signalling of TGF-β." Genes Cells. 3・9. 613-623 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto,D.,et al.: "A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3,and has a dominant negative effect on TGF-β signals." FEBS Lett. 430・3. 201-204 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inoue,H.,et al.: "Interplay of signal mediators of Dpp : Molecular characterization of Mothers against dpp,Medea.and Daughters against Dpp." Mol.Biol.Cell. 9・8. 2145-2156 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawabata,M.,et al.: "Smad proteins exist as monomers in vivo and undergo homo-and hetero-oligomerization uponactivation by serne/threonine kinase receptors." EMBO J.17・14. 4056-4065 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lu,S.-L.,et al.: "HNPCC associated with germline mutation in the TGF-β type II receptor gene." Nat.Genet.19・1. 17-18 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Imamura, T., et al.: "Smad6 inhibits signalling by the TGF-beta superfamily" Nature. 389-6651. 622-626 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakao, A., et al.: "Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling." Nature. 389-6651. 631-635 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakao, A., et al.: "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4." EMBO J.16-17. 5353-5362 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Beppu, H., et al.: "cDNA cloning and genomic organization of the mouse BMP type II receptor." Biochem. Biophys. Res. Commun.235-3. 499-504 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu, A., et al.: "Identification of receptors and Smad proteins involved in activin-signals in human epidermal keratinocytes." Genes Cells.3-2. 125-134 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takase, M., et al.: "Induction of Smad6 mRNA by bone morphogenetic proteins." Biochem. Biophys. Res. Commun.244-1. 26-29 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishihara, A., et al.: "Role of p300, a transcriptional coactivator, in signalling of TGF-beta." Genes Cells.3-9. 613-623 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto, D., et al.: "A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF-beta signals." FEBS Lett.430-3. 201-204 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inoue, H., et al.: "Interplay of signal mediators of Dpp : Molecular characterization of Mothers against dpp, Medea, and Daughters against Dpp." Mol. Biol. Cell.9-8. 2145-2156 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawabata, M., et al.: "Smad proteins exist as monomers in vivo and undergo homoand hetero-oligomerization upon activation by serine/threonine kinase receptors." EMBO J.17-14. 4056-4065 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lu, S.-L., et al.: "HNPCC associated with germline mutation in the TGF-beta type II receptor gene." Nat. Genet.19-1. 17-18 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagisawa, J., et al.: "Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators." Science. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagisawa,J., et al.: "Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators." Science. 印刷中.

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishihara,A., et al.: "Role of p300, a transcriptional coactivator, in signalling of TGF-β." Genes Cells. 3・9. 613-623 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Goto,D., et al.: "A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF-β signals." FEBS Lett. 430・3. 201-204 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue,H., et al.: "Interplay of signal mediators of Dpp : Molecular characterization of Mothers against dpp, Medea, and Daughters against Dpp." Mol.Biol.Cell. 9・8. 2145-2156 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawabata,M., et al.: "Smad proteins exist as monomers in vivo and undergo homo-and hetero-oligomerization upon activation by serine/threonine kinase receptors." EMBO J.17・14. 4056-4065 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lu,S-L., et al.: "HNPCC associated with germline mutation in the TGF-β type II receptor gene." Nat.Genet.19・1. 17-18 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Imamura T., Takase,M., Miyazono,K.,et al.: "Smad6 inhibits signalling by the TGF-β superfamily." Nature. 389・6651. 622-626 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao,A., Afrakhte,M., Moren,A.,et al.: "Identification of Smad7,a TGF-β-inducible antagonist of TGF-β signalling." Nature. 389・6651. 631-635 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao,A., Imamura,T., Miyazono,K.,et al.: "TGF-β receptor-mediated signalling through Smad2,Smad3 and Smad4." EMBO Journal. 16・17. 5353-5362 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Beppu,H., Kawabata,M., Miyazono,K.,et al.: "cDNA cloning and genomic organization of the mouse BMP type II receptor." Biochem.Biophys.Res.Commun.235・3. 499-504 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimizu,A., Kato,M., Miyazono,K.,et al.: "Identification of receptors and Smad proteins involved in activin signaling in a human epidermal keratinocyte cell line." Genes to Cells. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takase,M., Imamura,T., Miyazono,K.,et al.: "Induction of Smad6 mRNA by bone morphogenetic proteins." Biochem.Biophys.Res.Commun.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi