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

22 Citations (Scopus)

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 1 2012
Externally publishedYes

Fingerprint

Cytoplasmic and Nuclear Receptors
Breast Neoplasms
Estrogen Receptors
Orphan Nuclear Receptors
Tamoxifen
Transcription Factors
Gene Expression
Recurrence
Survival
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. / Park, Yun Yong; Kim, Kyounghyun; Kim, Sang Bae; Hennessy, Bryan T.; Kim, Soo Mi; Park, Eun Sung; Lim, Jae Yun; Li, Jane; Lu, Yiling; Gonzalez-Angulo, Ana Maria; Jeong, Woojin; Mills, Gordon; Safe, Stephen; Lee, Ju Seog.

In: EMBO Molecular Medicine, Vol. 4, No. 1, 01.01.2012, p. 52-67.

Research output: Contribution to journalArticle

Park, YY, Kim, K, Kim, SB, Hennessy, BT, Kim, SM, Park, ES, Lim, JY, Li, J, Lu, Y, Gonzalez-Angulo, AM, Jeong, W, Mills, G, Safe, S & Lee, JS 2012, 'Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer', EMBO Molecular Medicine, vol. 4, no. 1, pp. 52-67. https://doi.org/10.1002/emmm.201100187
Park, Yun Yong ; Kim, Kyounghyun ; Kim, Sang Bae ; Hennessy, Bryan T. ; Kim, Soo Mi ; Park, Eun Sung ; Lim, Jae Yun ; Li, Jane ; Lu, Yiling ; Gonzalez-Angulo, Ana Maria ; Jeong, Woojin ; Mills, Gordon ; Safe, Stephen ; Lee, Ju Seog. / Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. In: EMBO Molecular Medicine. 2012 ; Vol. 4, No. 1. pp. 52-67.
@article{a0881b4f8b024f4bbe31c953ef6ba735,
title = "Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer",
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.",
keywords = "Breast cancer, Genomics, Microarray, NR2E3, Nuclear receptor",
author = "Park, {Yun Yong} and Kyounghyun Kim and Kim, {Sang Bae} and Hennessy, {Bryan T.} and Kim, {Soo Mi} and Park, {Eun Sung} and Lim, {Jae Yun} and Jane Li and Yiling Lu and Gonzalez-Angulo, {Ana Maria} and Woojin Jeong and Gordon Mills and Stephen Safe and Lee, {Ju Seog}",
year = "2012",
month = "1",
day = "1",
doi = "10.1002/emmm.201100187",
language = "English (US)",
volume = "4",
pages = "52--67",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer

AU - Park, Yun Yong

AU - Kim, Kyounghyun

AU - Kim, Sang Bae

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

AU - Jeong, Woojin

AU - Mills, Gordon

AU - Safe, Stephen

AU - Lee, Ju Seog

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

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

KW - NR2E3

KW - Nuclear receptor

UR - http://www.scopus.com/inward/record.url?scp=84855228591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855228591&partnerID=8YFLogxK

U2 - 10.1002/emmm.201100187

DO - 10.1002/emmm.201100187

M3 - Article

C2 - 22174013

AN - SCOPUS:84855228591

VL - 4

SP - 52

EP - 67

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 1

ER -