title: Analysis of the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human ovarian carcinoma BG-1 cells.
abstract: We have used human ovarian carcinoma BG-1 cells to determine which steps in the pathway of estrogen signaling are disrupted by the aryl hydrocarbon receptor (AhR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We report that inhibition of estrogen signaling occurs between 7 and 18 h after TCDD treatment and that this effect is not caused by a decrease in estradiol concentration. TCDD decreased estrogen receptor (ER) levels in cells grown in standard medium; however, in estrogen-stripped medium, ER (but not AhR) levels were dramatically reduced (approximately 7-fold) but were not decreased further by TCDD. Because the absolute level of estradiol inducibility and inhibition by TCDD was similar in either medium, decreases in ER are not responsible for the antiestrogenic effect. The AhR also did not bind to the estrogen-responsive element (ERE) in vitro, and ERE binding by nuclear ER complexes was not decreased by TCDD, indicating that the effect of TCDD does not involve direct competition between the AhR and ER for DNA binding. However, inhibition of protein synthesis by cycloheximide blocked the TCDD-induced inhibition of ER-dependent gene expression. Overall, our results are consistent with the action of a TCDD-induced protein at a step(s) after ER-DNA binding, most likely at the level of gene transcription.
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, California 95616-8588, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Rogers
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000502:physiology; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013723:Teratogens / Q000494:pharmacology*; D014162:Transfection; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D000072317:Polychlorinated Dibenzodioxins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; C436317:RBM14 protein, human; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D013723:Teratogens; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D004247:DNA; D008156:Luciferases