Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells.

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 gamma-secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment. Knockdown of beta-catenin increased levels of Ah receptor mRNA, which may be attributable to direct or indirect involvement of beta-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. beta-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.