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Transcriptional Regulation of Selectin-ligand Synthetase (Fucosyltransferase VII) Related to Ability of Metastasis in Cancer Cells

Research Project

Project/Area Number 13670582
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionAichi Cancer Center

Principal Investigator

HIRAIWA Nozomu  Aichi Cancer Center, Molecular Pathology, Senior Associate, 分子病態学部, 主任研究員 (70175553)

Co-Investigator(Kenkyū-buntansha) KANNAGI Reiji  Head, 分子病態学部, 部長 (80161389)
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: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsSelectin-ligand / fucosyltransferase VII / Tax / CRE / T-box / one-hybrid / CREB / ATF / T-bet / fucosyltransferrase VII / One-hybrid法 / F7CAF-1
Research Abstract

Fucosyltransferase VII (Fuc-T VII) gene encodes a leukocyte/endothelial cell adhesion molecule -ligand sialyl Lewis X synthetase, the expression of which plays important roles in inflammation and even in metastasis of some cancer cells. We have shown that leukemia cells in patients with adult T-cell leukemia strongly express the sialyl Lewis X, the expression level of which significantly correlates with the degree of extravascular infiltration of the leukemic cells, and that the Fuc-T VII gene is transactivated by the HTLV-1 Tax.
We identified the Tax-responsive element (TaxRE) in the promoter of the Fuc-T VII gene, which contains a half-palindromic cAMP-responsive element (CRE). We found that several members of the CREB/ATF family and unidentified factors bind to this TaxRE being much homologous to the Tax-responsive viral CRE in the HTLV-1 long terminal repeat-promoter. In addition to the structural similarity, reporter analysis revealed that the TaxRE also bears functional resemblance to the viral CRE, differing from cellular CREs such as ** the somatostatin gene promoter.
To clarify the mechanism of such fransactivation in the TaxRE, we utilized the yeast one-hybrid system to clone cDNAs encoding TaxRE-binding factors involved in this transactivation. Besides members of CREB/ATF family, one cDNA was identified as the human homologue of one of the transcription factor T box family, T-bet, T-bet reportedly plays a critical role in differentiation of T lymphocyte to Th1. However, the exact binding sequence of T-bet and the mechanism of transactivation remain to be studied. We showed that T-bet actually binds to the 5' part of the TaxRE and also associates with Tax in vivo, and that T-bet is involved in the regulation of the Fuc-T VII gene in association with CREB/ATF family and Tax. These results suggest an important role for T-bet in HTLV-1 Tax-mediated Fuc-T VII gene transactivation.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Hiraiwa, N., et al.: "Transactivation of the fucosyltransferase VII gene by human T-cell leukemia virus type 1 tax through a variant cAMP-responsive element"Blood. (in print).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tei, K., et al.: "Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats"Cancer Res. 62. 6289-6296 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Schakel, K., et al.: "6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells"Immunity. 17. 283-301 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchimura, K., et al.: "Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression"J.Biol.Chem.. 277. 3979-3984 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kannnagi, R., et al.: "Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes"Curr.Opin.Struct.Biol.. 12. 599-608 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikeda, N., et al.: "A remodeling system of the 3'-sulfo-Lewis a and 3'-sulfo-Lewis x epitopes"J.Biol.Chem.. 276. 38588-38594 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiraiwa, N., et al.: "Transactivatton of the fucosyltransferase VII gene by human T-cell leukemia virus type 1 tax through a variant cAMP-responsive element"Blood. in print.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tei, K, et al.: "Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats"Cancer Res.. 62. 6289-6296 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Schakel, K., et al.: "6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells"Immunity. 17. 289-301 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchimura, K., et al.: "Specificities of N- acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression"J. Biol. Chem.. 277. 3979-3984 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kannnagi, R., et al.: "Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes"Curr. Opin. Struct. Biol.. 12. 599-608 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikeda, N., et al.: "A remodeling system of the 3'-sulfo-Lewis a and 3'-sulfo-Lewis x epitopes"J. Biol. Chem.. 276. 38588-38594 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumamoto, K., et al.: "Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants"Cancer Res.. 61. 4620-4627 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, K., et al.: "Paired tumor marker of soluble E-selectin and its ligand sialyl Lewis A in colorectal cancer"J Gastroenterol.. 36. 823-829 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiraiwa, N. et al.: "Tansactivation of the fucosyltransferase VII gene by human T-cell leukemia virus type 1 tax through a variant cAMP-responsive"Blood. (in print).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tei, K., et al.: "Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats"Cancer Res.. 62. 6289-6296 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Schakel, K., et al.: "6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells"Immunity. 17. 289-301 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchimura, K. et al.: "Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand-synthesis and tumor-associated enzyme"J. Biol. Chem.. 277. 3976-3984 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kannnagi, R., et al.: "Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes"Curr. Opin. Struct. Biol.. 12. 599-608 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, N., et al.: "A remodeling system of the 3'-sulfo-Lewis a and 3'-sulfo-Lewis x epitopes"J. Biol. Chem.. 276. 38588-38594 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchimura, K., et al.: "Specificities of N-acetylglucosamine-6-O-sulfofransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression"J.Biol.Chem.. 277. 3979-3984 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kontani, K., et al.: "Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes"Br.J.Cancer. 84. 1258-1264 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohmori, K., et al.: "P-and E-selectins recognize sialyl 6-sulfo lewis X, the recently identified L-selectin ligand"Biochem.Biophys.Res.Commun.. 278. 90-96 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Izawa, M., et al.: "Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer"Cancer Res.. 60. 1410-1416 (2000)

    • Related Report
      2001 Annual Research Report

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

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