Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Breast Neoplasms / enzymology
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cysteine Endopeptidases / metabolism*
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Down-Regulation / drug effects
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Environmental Pollutants / pharmacology
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Enzyme Activation / drug effects
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Estradiol / pharmacology
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Estrogen Receptor Modulators / pharmacology
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Estrogen Receptor alpha
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Humans
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Multienzyme Complexes / antagonists & inhibitors
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Multienzyme Complexes / metabolism*
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Polychlorinated Dibenzodioxins / pharmacology
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Proteasome Endopeptidase Complex
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Receptor Cross-Talk / drug effects
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Receptors, Aryl Hydrocarbon / agonists
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Receptors, Aryl Hydrocarbon / metabolism*
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Receptors, Estrogen / agonists
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Receptors, Estrogen / metabolism*
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Tumor Cells, Cultured
Substances
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Environmental Pollutants
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Estrogen Receptor Modulators
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Estrogen Receptor alpha
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Multienzyme Complexes
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Polychlorinated Dibenzodioxins
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Receptors, Aryl Hydrocarbon
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Receptors, Estrogen
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Estradiol
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex