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

EMBO Molecular Medicine

Yun-Yong Park¹  Kyounghyun Kim²  Sang-Bae Kim¹  Bryan T. Hennessy¹  Soo Mi Kim¹  Eun Sung Park¹  Jae Yun Lim¹  Jane Li¹  Yiling Lu¹  Ana Maria Gonzalez-Angulo¹  Woojin Jeong¹  Gordon B. Mills¹  Stephen Safe² 

[1] Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA;Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA

关键词: breast cancer;    genomics;    microarray;    NR2E3;    nuclear receptor;   

DOI  :  10.1002/emmm.201100187

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
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