Abstract
The effects of estrogen receptor (ER) ligands on the stability and transcriptional activity of ERbeta in the breast cancer cell lines MCF-7 and HeLa were examined. We found that ERbeta was degraded in the presence of 17beta-estradiol. Tamoxifen and Faslodex (ICI 182,780) prevented ERbeta receptor destabilization. In contrast to ERalpha, ERbeta degradation was not abolished by inhibitors of the proteasome-mediated protein degradation pathway. Furthermore, single point mutations in helix 12 of the receptor dramatically affected the stability and subsequent transcriptional activation of ERbeta.
MeSH terms
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Acetylcysteine / analogs & derivatives*
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Acetylcysteine / metabolism
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Animals
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Cysteine Proteinase Inhibitors / metabolism
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Estradiol / analogs & derivatives*
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Estradiol / metabolism*
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Estradiol / pharmacology
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Estrogen Antagonists / metabolism*
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Estrogen Receptor alpha / chemistry
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism*
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Estrogen Receptor beta / chemistry
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / metabolism*
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Female
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Fulvestrant
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Gene Expression Regulation
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Genes, Reporter
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Humans
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Ligands
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Point Mutation
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Tamoxifen / metabolism
Substances
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Cysteine Proteinase Inhibitors
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Estrogen Antagonists
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Ligands
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Tamoxifen
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lactacystin
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Fulvestrant
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Estradiol
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Acetylcysteine