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Biological function of Ah receptor

Research Project

Project/Area Number 17590112
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

IKUTA Togo  Institute for Clinical Oncology, Saitama Cancer Center, Researcher, 臨床腫瘍研究所, 主任研究員 (00262072)

Co-Investigator(Kenkyū-buntansha) KOIKE Manabu  Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, Researcher, 生体影響機構, 研究員 (70280740)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsskin / keratinocyte / epidermal-mesenchymal transition / wound healing / 上皮-間葉転換 / ダイオキシン / Ah receptor / keratinocyte / wound healing / Slug
Research Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which was initially identified as an intracellular mediator of the xenobiotic signaling pathway. We previously showed that AhR localizes predominantly in the cytoplasm under high cell densities of a keratinocytes cell line, HaCaT, but accumulates in the nucleus at low cell densities through modulation of its nuclear export activity. In the current report, we show that the Slug, which is a member of the snail/slug family of zinc finger transcriptional repressors critical for induction of epithelial-mesenchymal transitions (EMT), is activated transcriptionally in accordance with nuclear accumulation of AhR. By reporter assay of the promoter of the Slug gene, gel shift and chromatin immunoprecipitation analyses showed that AhR directly binds to xenobiotic responsive element 5 at-0.7 kb of the gene. AhR-targeted gene silencing by small interfering RNA duplexes led to the abolishment of not only CYP1A1 but also Slug induction by 3-methycholanthrene. The Slug was co-localized to the AhR at the wound margins of HaCaT cells, where apparent nuclear distribution of AhR and Slug was observed. The induced Slug was associated with reduction of an epithelial marker of cytokeratin-18 and with an increase in the mesenchymal marker, fibronectin. Surprisingly, TGF-β1-triggering EMT shows nuclear accumulation of AhR, suggesting that TGF-β-and AhR-directed EMTs share, in part, common molecular mechanisms. Taken together, these findings suggest that AhR participated in Slug induction, which, in turn, regulates cellular physiology including cell adhesion and migration.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2006 2005

All Journal Article (8 results)

  • [Journal Article] Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor2006

    • Author(s)
      Togo Ikuta
    • Journal Title

      Exp. Cell Res. 312

      Pages: 3585-3594

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Participation on nuclear localization signal 2 in the 3' -ETS domain of FLI1 in nuclear translocation of various chimeric EWS-FLI1 oncoproteins in Ewing tumor.2006

    • Author(s)
      Norikazu Honsei
    • Journal Title

      Int. J. Oncol. 29

      Pages: 689-693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor.2006

    • Author(s)
      Togo Ikuta et al.
    • Journal Title

      Exp. Cell Res. 312

      Pages: 3585-3594

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Participation on nuclear localization signal 2 in the 3'-ETS domain of FLU in nuclear translocation of various chimeric EWS-FLI1 oncoproteins in Ewing tumor.2006

    • Author(s)
      Norikazu Honsei et al.
    • Journal Title

      Int. J. Oncol. 29

      Pages: 689-693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor2006

    • Author(s)
      Togo Ikuta st al.
    • Journal Title

      Exp.Cell Res. 312

      Pages: 3585-3594

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Growth suppression of leydig TM3 cells mediated by aryl hydrocarbon receptor.2005

    • Author(s)
      Minoru Iseki
    • Journal Title

      Biochem. Biophys. Res. Commun. 331

      Pages: 902-908

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Growth suppression of leydig TM3 cells mediated by aryl hydrocarbon receptor.2005

    • Author(s)
      Minoru Iseki et al.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Pages: 902-908

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor2005

    • Author(s)
      Minoru Iseki et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 331

      Pages: 902-908

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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