Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer

Yun Yong Park, Kyounghyun Kim, Sang Bae Kim, Bryan T. Hennessy, Soo Mi Kim, Eun Sung Park, Jae Yun Lim, Jane Li, Yiling Lu, Ana Maria Gonzalez-Angulo, Woojin Jeong, Gordon Mills, Stephen Safe, Ju Seog Lee

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)52-67
Number of pages16
JournalEMBO Molecular Medicine
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

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Keywords

  • Breast cancer
  • Genomics
  • Microarray
  • NR2E3
  • Nuclear receptor

ASJC Scopus subject areas

  • Molecular Medicine

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