Open AccessReconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer
Author(s) -
Park YunYong,
Kim Kyounghyun,
Kim SangBae,
Hennessy Bryan T.,
Kim Soo Mi,
Park Eun Sung,
Lim Jae Yun,
Li Jane,
Lu Yiling,
GonzalezAngulo Ana Maria,
Jeong Woojin,
Mills Gordon B.,
Safe Stephen,
Lee JuSeog
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100187
Subject(s) - estrogen receptor alpha , breast cancer , estrogen receptor , tamoxifen , nuclear receptor , cancer research , regulator , biology , cancer , transcription factor , gene , genetics
ESR1 is one of the most important transcription factors and therapeutic targets in breast cancer. By applying systems‐level re‐analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1 . We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to the promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)‐positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence‐free survival and a favourable response to tamoxifen treatment in women with ER‐positive breast cancer. Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer.