β-Catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells

Shuya Kasai, Takanori Ishigaki, Ryo Takumi, Toru Kamimura, Hideaki Kikuchi

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Background The aryl hydrocarbon (Ah) receptor is one of the best known ligand-activated transcription factors. The present study has focused on the wound-healing process on Ah receptor function. Methods Depletion of calcium from culture medium of Caco-2 human colon carcinoma cells by transfer to Minimal Essential Medium (Spinner Modification; S-MEM) destroyed adherens junctions and the cells were used as the model of wound-healing process. Results Calcium depletion induced both nuclear translocation of the Ah receptor, and increased expression of CYP1A1 and Slug mRNAs in Caco-2 cells. However, expression of Slug mRNA was not significantly induced by treatment with 2,3,7,8- tetrachlorodibenzo-p-dioxin. Knockdown of the Ah receptor and treatment with Ah receptor antagonists decreased level of CYP1A1 mRNA. The fragment of E-cadherin released by γ-secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment. Knockdown of β-catenin increased levels of Ah receptor mRNA, which may be attributable to direct or indirect involvement of β-catenin in suppression of the Ah receptor gene. Conclusions Our results suggest that mRNA induction of some genes by destruction of adherens junctions depends on the Ah receptor. β-Catenin, one of the components of the adherens junction, was released from the E-cadherin complex, which resulted in its increased interaction with the Ah receptor, and was translocated into the nucleus, and consequently the target genes would be transcribed. General significance Our observations suggest that some aspects of the molecular mechanism of wound healing involve the Ah receptor.

    Original languageEnglish
    Pages (from-to)2509-2516
    Number of pages8
    JournalBiochimica et Biophysica Acta - General Subjects
    Volume1830
    Issue number3
    DOIs
    Publication statusPublished - 2013 Mar

    Keywords

    • Aryl hydrocarbon receptor
    • Cytochrome P-450 1A1
    • E-cadherin
    • E-cadherin carboxy terminal fragment 2
    • S-MEM
    • β-Catenin

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology

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