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Summary: Altered Target Gene Regulation Controlled by
Estrogen Receptor- Concentration
Amy M. Fowler, Natalia M. Solodin, Christopher C. Valley, and Elaine T. Alarid
Department of Physiology, University of Wisconsin-Madison, Madison, Wisconsin 53706
Estrogen receptor- (ER ) is a transcriptional ac-
tivator whose concentration is tightly regulated by
the cellular environment. In breast tumors of post-
menopausal women, elevated receptor concentra-
tions can be associated with negative clinical out-
comes, yet it remains poorly understood how such
high levels impact ER function. We previously
demonstrated that high nuclear concentrations of
ER in breast cancer cells bypass the requirement
for ligand and are sufficient to activate transcrip-
tion and accelerate proliferation. Here, we ex-
tended those studies and asked whether the tran-
scriptional targets and activation mechanism are
similar or different from that of estrogen-stimu-
lated ER . We found that at elevated levels, ER
activated, but could not repress, known estrogen-
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