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

doi:10.1002/emmm.201100187

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 journal › Article › peer-review

36 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 language	English (US)
Pages (from-to)	52-67
Number of pages	16
Journal	EMBO Molecular Medicine
Volume	4
Issue number	1
DOIs	https://doi.org/10.1002/emmm.201100187
State	Published - Jan 2012
Externally published	Yes

Keywords

Breast cancer
Genomics
Microarray
NR2E3
Nuclear receptor

ASJC Scopus subject areas

Molecular Medicine

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10.1002/emmm.201100187

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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

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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.",

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AU - Hennessy, Bryan T.

AU - Kim, Soo Mi

AU - Park, Eun Sung

AU - Lim, Jae Yun

AU - Li, Jane

AU - Lu, Yiling

AU - Gonzalez-Angulo, Ana Maria

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AU - Mills, Gordon B.

AU - Safe, Stephen

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AB - 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.

KW - Breast cancer

KW - Genomics

KW - Microarray

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

Abstract

Keywords

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