Aryl Hydrocarbon Receptor Directly Regulates VTCN1 Gene Expression in MCF-7 Cells

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity of dioxins and polycyclic aromatic hydrocarbons. Recent studies have suggested that AhR is involved in cancer immunity. In the present study, we examined whether AhR regulates the expression of immune checkpoint genes in breast cancer cells. We discovered that the mRNA expression of V-set domain containing T cell activation inhibitor 1 (VTCN1) that negatively regulates T cell immunity was upregulated by AhR agonists in breast cancer cell lines, MCF-7 and T47D. Furthermore, AhR knockout or knockdown experiments clearly demonstrated that upregulation of VTCN1 gene expression by 3-methylcholanthrene was AhR dependent. Luciferase reporter and chromatin immunoprecipitation assays revealed that this upregulation of VTCN1 gene expression was induced by the recruitment of AhR to the AhR responsive element in the VTCN1 gene promoter in MCF-7 cells. Taken together, AhR directly regulates VTCN1 gene expression in MCF-7 cells.

Omeprazole Induces <i>CYP3A4</i> mRNA Expression but Not CYP3A4 Protein Expression in HepaRG Cells

“…Upon activation by rifampicin and omeprazole, PXR and AhR heterodimerize with the retinoic acid receptor α (RXRα) 21,22) or AhR nuclear translocator (ARNT), 23,24) forming a transcriptionally active complex. Previous chromatin immunoprecipitation assay demonstrated enrichment of RXRα 25) and AhR 26) at the CYP3A4 promoter region up to −10 kb upstream of the transcription start site (GSE127399 and GSE206029), which supports our observation of CYP3A4 mRNA induction by rifampicin and omeprazole.…”