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Analysis of E-cadherin-Dependent Contact Inhibition in Gastric Cancer Cell Line

Research Project

Project/Area Number 13670537
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

TERUI Takeshi  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助手 (50281233)

Co-Investigator(Kenkyū-buntansha) KATO Junji  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (20244345)
古川 勝久  札幌医科大学, 医学部, 講師 (60244349)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsContact Inhibition / γ-Catenin / p21 / WAF1 / Rho / 消火器癌 / 細胞増殖抑制 / E-カドヘリン / カテニン / WAF-1 / 消化器癌 / E-ガドヘリン
Research Abstract

To investigate the mechanism of contact inhibition, we cloned an adhesive subline HSC39Ad from parental non-adhesive HSC39 gastric cancer cell line, which has a deletion in the β-catenin gene (Mol Cell Biol 1995 Mar : 15(3) : 1175-81). This subline grew slower than the parental cells in vitro and in vivo. The neutralizing antibody of E-cadherin (HECD1) caused the lost of adhesive character of HSC39Ad cells, resulting in the enhancement of growth rate and the decrement of the expression of both p21/WAF1 and Rb in the dephosphorylated form. The same results were obtained by the specific antisense oligonucleotide against γ-catenin, which was expressed in HSC39Ad two-times higher than HSC39 cells. On the other hand, the treatment of HSC39Ad cells with HECD1 caused the activation of the small GTP-binding protein Rho. Further, C3, the inhibitor of Rho, restored both the enhancement of growth rate and the decrement of the expression of p21/WAF1 induced by HECD1 in HSC39 Ad cells. These results indicate that β-catenin bound with E-cadherin causes the signal transduction via Rho to p21/WAF1, resulting in the contact inhibition of HSC39 cells.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kato J, et al.: "Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet"Cancer Res. 61. 8697-8702 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato J, et al.: "A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload"Am J Hum Genet. 69. 191-197 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki E, et al.: "Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload"Gut. 50. 413-419 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki H, et al.: "Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1"J Immunol. 168. 5178-5183 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M, et al.: "E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor"Mol Ther. 5. 627-634 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato J, Kobune M, Nakamura T, Kuroiwa G, Takada K, Takimoto R, Sato Y, Fujikawa K, Takahashi M, Takayama T, Ikeda T, Niitsu Y: "Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet"Cancer Res. 61. 8697-8702 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyanishi K, Takayama T, Ohi M, Hayashi T, Nobuoka A, Nakajima T, Takimoto R, Kogawa K, Kato J, Sakamaki S, Niitsu Y: "Glutathione S-transferase-pi overexpression is closely associated with K-ras mutation during human colon carcinogenesis"Gastroenterology. 121. 865-874 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iyama S, Okamoto T, Sato T, Yamauchi N, Sato Y, Sasaki K, Takahashi M, Tanaka M, Adachi T, Kogawa K, Kato J, Sakamaki S, Niitsu Y: "Treatment of murine collagen-induced arthritis by ex vivo extracellular superoxide dismutase gene transfer"Arthritis Rheum. 44. 2160-2167 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takayama T, Ohi M, Hayashi T, Miyanishi K, Nobuoka A, Nakajima T, Satoh T, Takimoto R, Kato J, Sakamaki S, Niitsu Y: "Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis"Gastroenterology. 121. 599-611 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato J, Fujikawa K, Kanda M, Fukuda N, Sasaki K, Takayama T, Kobune M, Takada K, Takimoto R, Hamada H, Ikeda T, Niitsu Y: "A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload"Am J Hum Genet. 69. 191-197 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lu Y, Yamauchi N, Koshita Y, Fujiwara H, Sato Y, Fujii S, Takahashi M, Sato T, Kato J, Yamagishi H, Niitsu Y: "Administration of subtumor regression dosage of TNF-alpha to mice with pre-existing parental tumors augments the vaccination effect of TNF gene-modified tumor through the induction of MHC class I molecule"Gene Ther. 8. 499-507 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lu Y, Sakamaki S, Kuroda H, Kusakabe T, Konuma Y, Akiyama T, Fujimi A, Takemoto N, Nishiie K, Matsunaga T, Hirayama Y, Kato J, Kon S, Kogawa K, Niitsu Y: "Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603"Blood. 97. 1123-1130 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki H, Sato T, Yamauchi N, Okamoto T, Kobayashi D, Iyama S, Kato J, Matsunaga T, Takimoto R, Takayama T, Kogawa K, Watanabe N, Niitsu Y: "Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1"J Immunol. 168. 5178-5183 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M, Sato T, Sagawa T, Lu Y, Sato Y, Iyama S, Yamada Y, Fukaura J, Takahashi S, Miyanishi K, Yamashita T, Sasaki K, Kogawa K, Hamada H, Kato J, Niitsu Y: "ElB-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor"Mol Ther. 5. 627-634 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki E, Kato J, Kobune M, Okumura K, Sasaki K, Shintani N, Arosio P, Niitsu Y: "Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload"Gut. 50. 413-419 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M, Sato T, Sagawa T, Lu Y, Sato Y, lyama S, Yamada Y, Fukaura J, Takahashi S, Miyanishi K, Yamashita T, Sasaki K, Kogawa K, Kato J, Niitsu Y: "EIB-55K deleted adenovirus expressing EIA-13S by AFP enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor"Mol Ther.. 5. 627-634 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki E, Kato J, Kobune M, Okumura K, Sasaki K, Shintani N, Arosio P, Niitsu Y: "Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload"Gut. 50. 413-419 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawano Y, Kobune M, Yamaguchi M, Nakamura K, Ito Y, Sasaki K, Takahashi S, Nakamura T, Chiba H, Sato T, Matsunaga T, Azuma H, Ikebuchi K, Ikeda H, Kato J, Niitsu Y, Hamada H: "Ex vivo expansion of human umbilical cord hematopoijetic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells"Blood. 101. 532-540 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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