Human Gene Set: STEIN_ESRRA_TARGETS_RESPONSIVE_TO_ESTROGEN_DN


Standard name STEIN_ESRRA_TARGETS_RESPONSIVE_TO_ESTROGEN_DN
Systematic name M19002
Brief description Genes down-regulated by estradiol [PubChem=5757] and down-regulated by ESRRA [GeneID=2101] in MCF-7 cells (breast cancer).
Full description or abstract Expression of estrogen-related receptor alpha (ERRalpha) 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 alpha (ERalpha) and ERRalpha initially suggested that these receptors may have similar transcriptional targets. Using the well-characterized ERalpha-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ERalpha-ERRalpha cross-talk using an unbiased microarray approach. In addition to generating a host of novel ERRalpha target genes, this study yielded the surprising result that most ERRalpha-regulated genes are unrelated to estrogen signaling. The relatively small number of genes regulated by both ERalpha and ERRalpha led us to expand our study to the more aggressive and less clinically treatable ERalpha-negative class of breast cancers. In this setting, we found that ERRalpha expression is required for the basal level of expression of many known and novel ERRalpha target genes. Introduction of a small interfering RNA directed to ERRalpha into the highly aggressive breast carcinoma MDA-MB-231 cell line dramatically reduced the migratory potential of these cells. Although stable knockdown of ERRalpha 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 ERRalpha in breast cancer growth and highlight it as a potential therapeutic target for estrogen receptor-negative breast cancer.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18974123   Authors: Stein RA,Chang CY,Kazmin DA,Way J,Schroeder T,Wergin M,Dewhirst MW,McDonnell DP
Exact source Table 2S: Class 3 = CLASS 3
Related gene sets (show 6 additional gene sets from the source publication)

(show 5 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HG_U133
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 41 genes
Gene families ? Categorize these 41 genes by gene family
Show members (show 46 source identifiers mapped to 41 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.