Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors.
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.
Fuqua
S A
SA
Department of Medical Oncology, University of Texas Health Science Center, San Antonio 78284-7884.
Fitzgerald
S D
SD
Allred
D C
DC
Elledge
R M
RM
Nawaz
Z
Z
McDonnell
D P
DP
O'Malley
B W
BW
Greene
G L
GL
McGuire
W L
WL
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
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors