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 alpha-naphthoflavone and were not observed in Ah nonresponsive benzo[alpha]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 17 beta-estradiol (E2), there was a 2.3-fold increase in PRLR mRNA levels, and in cells cotreated 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.
Lu
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YF
Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
Sun
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Wang
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Safe
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D001571:Benzoflavones / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D001571:Benzoflavones; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D011981:Receptors, Prolactin; D004958:Estradiol; C011512:alpha-naphthoflavone