title: Variant human breast tumor estrogen receptor with constitutive transcriptional activity.
abstract: Since progesterone receptor (PgR) is normally induced by estrogen, breast cancer lacking estrogen receptor (ER) would also be expected to lack PgR. However, a small percentage of breast cancers are ER- yet PgR+. These tumors might possess an ER which is defective in estrogen binding but is still functional in stimulating estrogen-responsive genes such as PgR. We have now detected such a variant, lacking exon 5 of the hormone-binding domain, using complementary DNA amplified by the polymerase chain reaction. This variant was the predominate ER RNA expressed in three ER-/PgR+ tumors. Furthermore, the variant ER constitutively activates transcription of a normally estrogen-dependent gene construct in yeast cells. The variant ER could explain the expression of PgR in certain tumors and have therapeutic implications.
authors.affiliation: University of Texas Health Science Center, Department of Medical Oncology, 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: G C
authors.initials: GC
authors.lastname: Chamness
authors.forename: A K
authors.initials: AK
authors.lastname: Tandon
authors.forename: D P
authors.initials: DP
authors.lastname: McDonnell
authors.forename: Z
authors.initials: Z
authors.lastname: Nawaz
authors.forename: B W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: W L
authors.initials: WL
authors.lastname: McGuire
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics* / Q000276:immunology; D011980:Receptors, Progesterone / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011994:Recombinant Proteins