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

Biochem Biophys Res Commun. 2004 Jul 16;320(1):76-82. doi: 10.1016/j.bbrc.2004.05.132.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Cycloheximide / pharmacology*
  • Estrogen Receptor beta
  • Estrogens / metabolism*
  • Humans
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Receptors, Estrogen / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Estrogen Receptor beta
  • Estrogens
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Receptors, Estrogen
  • Cycloheximide