The Ah receptor inhibits estrogen-induced estrogen receptor beta 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) beta gene expression in the human breast cancer cell line, T47D. TCDD inhibited 17beta-estradiol (E2)-induced up-regulation of both ER beta wild type and ER beta cx mRNA. Cycloheximide pre-treatment had no inhibitory effect, and the estimated half-life of ER beta mRNA of about 33 min was not changed by any hormone administration. Chromatin immunoprecipitation experiments showed recruitment of ER alpha to the ER beta promoter. Gel mobility shift experiments revealed an E2-induced protein binding to a half site estrogen response element in the ER beta promoter, and TCDD reduced that binding. These results show that ER alpha regulates the expression of its own heterodimerization partner, ER beta, in T47D cells. TCDD, an anti-estrogenic compound, inhibits ER alpha-mediated induction of ER beta mRNA. These findings add to our understanding of cross talk between dioxin and estrogen signaling in human cells.
Kietz
Silke
S
Department of Bioscience at NOVUM, Karolinska Institutet, S-141 57 Huddinge, Sweden. silkekietz@yahoo.de
Thomsen
Jane S
JS
Matthews
Jason
J
Pettersson
Katarina
K
Ström
Anders
A
Gustafsson
Jan-Ake
JA
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D047629:Estrogen Receptor beta; D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D003513:Cycloheximide