The Ah receptor inhibits estrogen-induced estrogen receptor β in breast cancer cells

We have studied the effect of the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrogen receptor (ER) β gene expression in the human breast cancer cell line, T47D. TCDD inhibited 17β-estradiol (E₂)-induced up-regulation of both ER β wild type and ER β cx mRNA. Cycloheximide pre-treatment had no inhibitory effect, and the estimated half-life of ER β mRNA of about 33min was not changed by any hormone administration. Chromatin immunoprecipitation experiments showed recruitment of ER α to the ER β promoter. Gel mobility shift experiments revealed an E₂-induced protein binding to a half site estrogen response element in the ER β promoter, and TCDD reduced that binding. These results show that ER α regulates the expression of its own heterodimerization partner, ER β, in T47D cells. TCDD, an anti-estrogenic compound, inhibits ER α-mediated induction of ER β mRNA. These findings add to our understanding of cross talk between dioxin and estrogen signaling in human cells.