%0 Journal Article
%T Estrogen-related receptor alpha: an orphan finds a family
%A Aleksandra M Ochnik
%A Douglas Yee
%J Breast Cancer Research
%D 2012
%I BioMed Central
%R 10.1186/bcr3124
%X Nuclear receptors (NRs) are well accepted as critical mediators in many aspects of breast cancer pathogenesis. Molecular cloning of estrogen receptor alpha (ER¦Á) has demonstrated how molecular targeting of specific domains of a single protein can improve outcomes. Molecular cloning techniques have revealed receptors related to ER¦Á, including the 'estrogen-related receptor' (ERR) family.Recent prognostic studies have demonstrated that overexpression of one of these family members, ERR¦Á, is associated with a poor outcome in patients with ER- breast cancer [1], yet the transcriptional regulation of the orphan receptor ERR¦Á is still not well known. Overexpression of ERR¦Á has been shown to be associated with elevated human epidermal growth factor 2 (HER2) expression [2], and ERR¦Á can interact with the co-regulators PGC-1 ¦Á and ¦Â (peroxisome proliferator-activated gamma co-activator-1 alpha and beta) [3,4] in addition to a number of p160 co-activators [5,6]. Interestingly, ERR¦Á displays distinct subtype transcriptional activation that is not similarly identified by ER [7]. Unlike ER¦Á, which has been targeted by ligand deprivation (oophorectomy and aromatase inhibitors) and selective estrogen receptor modulators (tamoxifen and fulvestrant), ERR¦Á has no known ligand and therefore is not amenable to drug inhibition in the same fashion.If ERR¦Á regulates breast cancer cells, then we need to understand its mechanism of action. Since there are no known ways to target ERR¦Á+ ER- breast cancers, molecular techniques could be used (a) to gain an understanding of how ERR¦Á modulates gene expression in breast cancer subtypes [8-11] and (b) to develop potential therapeutic approaches to target ERR¦Á-driven tumors [12].Chang and colleagues [12] created normal human mammary epithelial cell lines overexpressing ERR¦Á to better understand its transcriptional targets. Since no ligand exists for ERR¦Á, overexpression of the well-characterized co-regulator of ERR¦Á, PGC-1¦Á, was used to activate tr
%U http://breast-cancer-research.com/content/14/3/309