Crosstalk between estrogen receptor alpha and the aryl hydrocarbon receptor in breast cancer cells involves unidirectional activation of proteasomes.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways. T47D human breast cancer cells express a functional estrogen receptor alpha (ERalpha) and AhR, and treatment of these cells with 17beta-estradiol (E2) or TCDD resulted in a rapid proteasome-dependent decrease in immunoreactive ERalpha and AhR proteins (>60-80%), respectively. E2 did not affect the AhR, whereas TCDD induced proteasome-dependent degradation of both the AhR and ERalpha in T47D and MCF-7 human breast cancer cells, and these responses were specifically blocked by proteasome inhibitors. Thus, TCDD-induced degradation of ERalpha may contribute to the antiestrogenic activity of AhR agonists and this pathway may be involved in AhR-mediated disruption of other endocrine responses.
Wormke
M
M
Department of Veterinary Physiology and Pharmacology, and Department of Biochemistry and Biophysics, Texas A&M University, 77843-4466, College Station, TX, USA.
Stoner
M
M
Saville
B
B
Safe
S
S
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004785:Environmental Pollutants / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D020239:Receptor Cross-Talk / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004785:Environmental Pollutants; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D009097:Multienzyme Complexes; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D004958:Estradiol; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex