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 B. Mills, Stephen Safe, Ju Seog Lee

    Research output: Contribution to journalArticle

    26 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
    StatePublished - Jan 2012

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Medicine

    Fingerprint Dive into the research topics of 'Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Park, Y. Y., Kim, K., Kim, S. B., Hennessy, B. T., Kim, S. M., Park, E. S., Lim, J. Y., Li, J., Lu, Y., Gonzalez-Angulo, A. M., Jeong, W., Mills, G. B., Safe, S., & Lee, J. S. (2012). Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Molecular Medicine, 4(1), 52-67. https://doi.org/10.1002/emmm.201100187