INHIBITION OF PROLACTIN RECEPTOR GENE-EXPRESSION BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN MCF-7 HUMAN BREAST-CANCER CELLS

Treatment of MCF-7 human breast cancer cells with 10 nM 2,3,7,8-tetrac hlorodibenzo-p-dioxin (TCDD) did not decrease prolactin receptor (PRLR ) binding. In contrast, PRLR mRNA levels were significantly decreased within 12 h after treatment with TCDD and persisted for up to 48 h. Th e effects of TCDD on PRLR mRNA levels were inhibited by the aryl hydro carbon (Ah) receptor antagonist alpha-naphthoflavone and were not obse rved in Ah nonresponsive benzo[a]pyrene-resistant MCF-7 cells. These r esults suggest that the effects of TCDD were mediated through the Ah r eceptor. After treatment of MCF-7 cells with 10 nM 17 beta-estradiol ( E2), there was a 2.3-fold increase in PRLR mRNA levels, and in cells c otreated with E2 plus TCDD, there was a 72% decrease in E2-induced PRL R mRNA levels, Previous studies have showed that TCDD also effects est rogen receptor (ER) binding and mRNA levels through the aryl hydrocarb on receptor pathway; however, the effects of TCDD on PRLR levels and b inding in MCF-7 cells were different from those previously observed fo r ER. (C) 1996 Academic Press, Inc.