Human Gene Set: WILLIAMS_ESR1_TARGETS_UP


Standard name WILLIAMS_ESR1_TARGETS_UP
Systematic name M2970
Brief description The 'ER-alpha profile': genes up-regulated in T47D cells (breast cancer, ESR2 [GeneID=2100] Tet-Off) upon activation of ESR1 [GeneID=2099] by estradiol (E2) [PubChem=5757].
Full description or abstract Transcriptional effects of estrogen result from its activation of two estrogen receptor (ER) isoforms; ERalpha that drives proliferation and ERbeta that is antiproliferative. Expression of ERbeta in xenograft tumors from the T47D breast cancer cell line reduces tumor growth and angiogenesis. If ERbeta can halt tumor growth, its introduction into cancers may be a novel therapeutic approach to the treatment of estrogen-responsive cancers. To assess the complete impact of ERbeta on transcription, we have made a full transcriptome analysis of ERalpha- and ERbeta-mediated gene regulation in T47D cell line with Tet-Off regulated ERbeta expression. Of the 35 000 genes and transcripts analysed, 4.1% (1434) were altered by ERalpha activation. Tet withdrawal and subsequent ERbeta expression inhibited the ERalpha regulation of 998 genes and, in addition, altered expression of 152 non-ERalpha-regulated genes. ERalpha-induced and ERbeta-repressed genes were involved in proliferation, steroid/xenobiotic metabolism and ion transport. The ERbeta repressive effect was further confirmed by proliferation assays, where ERbeta was shown to completely oppose the ERalpha-E2 induced proliferation. Additional analysis of ERbeta with a mutated DNA-binding domain revealed that this mutant, at least for a quantity of genes, antagonizes ERalpha even more strongly than ERbeta wt. From an examination of the genes regulated by ERalpha and ERbeta, we suggest that introduction of ERbeta may be an alternative therapeutic approach to the treatment of certain cancers.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17700529   Authors: Williams C,Edvardsson K,Lewandowski SA,Ström A,Gustafsson JA
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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Version history 3.0: First introduced

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