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- tetrachlorodibenzo-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. The effects of TCDD on PRLR mRNA levels were inhibited by the aryl hydrocarbon (Ah) receptor antagonist α-naphthoflavone and were not observed in Ah nonresponsive benzo[a]pyrene-resistant MCF-7 cells. These results suggest that the effects of TCDD were mediated through the Ah receptor. After treatment of MCF-7 cells with 10 nM 17β-estradiol (E2), there was a 2.3-fold increase in PRLR mRNA levels, and in cells cotteated with E2 plus TCDD, there was a 72% decrease in E2-induced PRLR mRNA levels. Previous studies have showed that TCDD also effects estrogen receptor (ER) binding and mRNA levels through the aryl hydrocarbon receptor pathway; however, the effects of TCDD on PRLR levels and binding in MCF-7 cells were different from those previously observed for ER.