title: Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors.
abstract: It is fairly well accepted that the presence of estrogen receptor (ER) and progesterone receptor (PgR) identifies breast cancer patients with a lower risk of relapse and better overall survival. But patients with discordant receptors, the ER+/PgR- phenotype, are often intermediate in clinical response. We focused upon this group of patients and have identified a truncated ER which is abundant in some ER+/PgR- breast tumors and which inhibits the binding of wild-type ER to its cognate response element. This variant interferes in a dominant negative manner with wild-type ER function and may represent a mechanism for modulation of estrogen responsiveness.
authors.affiliation: Department of Medical Oncology, University of Texas Health Science Center, San Antonio 78284-7884.
authors.forename: S A
authors.initials: SA
authors.lastname: Fuqua
authors.forename: S D
authors.initials: SD
authors.lastname: Fitzgerald
authors.forename: D C
authors.initials: DC
authors.lastname: Allred
authors.forename: R M
authors.initials: RM
authors.lastname: Elledge
authors.forename: Z
authors.initials: Z
authors.lastname: Nawaz
authors.forename: D P
authors.initials: DP
authors.lastname: McDonnell
authors.forename: B W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: G L
authors.initials: GL
authors.lastname: Greene
authors.forename: W L
authors.initials: WL
authors.lastname: McGuire
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics* / Q000502:physiology; D011980:Receptors, Progesterone / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors