This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stein, R. A. Articles by McDonnell, D. P. Search for Related Content PubMed PubMed Citation Articles by Stein, R. A. Articles by McDonnell, D. P.

Estrogen-Related Receptor Is Critical for the Growth of Estrogen Receptor–Negative Breast Cancer

¹ Department of Pharmacology and Cancer Biology and ² Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina and ³ GlaxoSmithKline, Research Triangle Park, North Carolina

Requests for reprints: Donald P. McDonnell, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710. Phone: 919-684-6035; Fax: 919-681-7139; E-mail: donald.mcdonnell{at}duke.edu.

Key Words: estrogen-related receptor • breast cancer • ESRRA

Expression of estrogen-related receptor (ERR) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of this orphan nuclear receptor in tumor growth and progression, however, is yet to be fully understood. The significant homology between estrogen receptor (ER) and ERR initially suggested that these receptors may have similar transcriptional targets. Using the well-characterized ER-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ER-ERR cross-talk using an unbiased microarray approach. In addition to generating a host of novel ERR target genes, this study yielded the surprising result that most ERR-regulated genes are unrelated to estrogen signaling. The relatively small number of genes regulated by both ER and ERR led us to expand our study to the more aggressive and less clinically treatable ER-negative class of breast cancers. In this setting, we found that ERR expression is required for the basal level of expression of many known and novel ERR target genes. Introduction of a small interfering RNA directed to ERR into the highly aggressive breast carcinoma MDA-MB-231 cell line dramatically reduced the migratory potential of these cells. Although stable knockdown of ERR expression in MDA-MB-231 cells had no effect on in vitro cell proliferation, a significant reduction of tumor growth rate was observed when these cells were implanted as xenografts. Our results confirm a role for ERR in breast cancer growth and highlight it as a potential therapeutic target for estrogen receptor–negative breast cancer. [Cancer Res 2008;68(21):8805–12]

This article has been cited by other articles:

				G. Deblois, J. A. Hall, M.-C. Perry, J. Laganiere, M. Ghahremani, M. Park, M. Hallett, and V. Giguere Genome-Wide Identification of Direct Target Genes Implicates Estrogen-Related Receptor {alpha} as a Determinant of Breast Cancer Heterogeneity Cancer Res., August 1, 2009; 69(15): 6149 - 6157. [Abstract] [Full Text] [PDF]

				S. Heck, J. Rom, V. Thewes, N. Becker, B. Blume, H. P. Sinn, U. Deuschle, C. Sohn, A. Schneeweiss, and P. Lichter Estrogen-Related Receptor {alpha} Expression and Function Is Associated with the Transcriptional Coregulator AIB1 in Breast Carcinoma Cancer Res., June 15, 2009; 69(12): 5186 - 5193. [Abstract] [Full Text] [PDF]

				V. C. Jordan A Century of Deciphering the Control Mechanisms of Sex Steroid Action in Breast and Prostate Cancer: The Origins of Targeted Therapy and Chemoprevention Cancer Res., February 15, 2009; 69(4): 1243 - 1254. [Abstract] [Full Text] [PDF]