title: Distinct effects of the antiestrogen Faslodex on the stability of estrogen receptors-alpha and -beta in the breast cancer cell line MCF-7.
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.
authors.affiliation: Department of Atherosclerosis and Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA. norbert_peekhaus@merck.com
authors.forename: N T
authors.initials: NT
authors.lastname: Peekhaus
authors.forename: T
authors.initials: T
authors.lastname: Chang
authors.forename: E C
authors.initials: EC
authors.lastname: Hayes
authors.forename: H A
authors.initials: HA
authors.lastname: Wilkinson
authors.forename: S W
authors.initials: SW
authors.lastname: Mitra
authors.forename: J M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: S P
authors.initials: SP
authors.lastname: Rohrer
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D017354:Point Mutation; D013629:Tamoxifen / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D013629:Tamoxifen; C067713:lactacystin; D000077267:Fulvestrant; D004958:Estradiol; D000111:Acetylcysteine