title: Identification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen.
abstract: We have generated mutant mouse estrogen receptors which differ in their sensitivity to estrogen and the antiestrogen 4-hydroxytamoxifen. Mutation of the glycine at position 525 and the methionine and/or serine at positions 521/522 virtually abolishes the ability of the receptor to bind estradiol and stimulate transcription. In contrast, the mutant receptors retain the partial agonist activity exhibited by the wild-type receptor in the presence of 4-hydroxytamoxifen. The mutations do not affect the expression and DNA-binding activity of the receptor, but do abolish the estrogen-induced increase in the mobility of the receptor-DNA complex observed with the wild-type receptor. Other mutant receptors that were able to bind and stimulate transcription in the presence of estradiol also failed to show the agonist-induced increase in the mobility of the receptor-DNA complex, suggesting that it is unlikely to reflect the formation of a hormone-dependent transcriptional activation function.
authors: Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
authors: P S
authors: PS
authors: Danielian
authors: R
authors: R
authors: White
authors: S A
authors: SA
authors: Hoare
authors: S E
authors: SE
authors: Fawell
authors: M G
authors: MG
authors: Parker
mesh_terms: D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D051379:Mice; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D011955:Receptors, Drug; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D004247:DNA