Human Gene Set: BHAT_ESR1_TARGETS_VIA_AKT1_DN


Standard name BHAT_ESR1_TARGETS_VIA_AKT1_DN
Systematic name M2235
Brief description Genes bound by ESR1 [GeneID=2099] and down-regulated by estradiol [PubChem=5757] in MCF-7 cells (breast cancer) expressing constitutevly active form of AKT1 [GeneID=207].
Full description or abstract Estrogen regulates several biological processes through estrogen receptor alpha (ERalpha) and ERbeta. ERalpha-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERalpha binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERalpha binding sites, respectively, with approximately 60% overlap. In both cell types, approximately 40% of estrogen-regulated genes associate with ERalpha binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor beta (TGF-beta), NF-kappaB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-beta treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERalpha DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERalpha binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERalpha-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERalpha-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18838536   Authors: Bhat-Nakshatri P,Wang G,Appaiah H,Luktuke N,Carroll JS,Geistlinger TR,Brown M,Badve S,Liu Y,Nakshatri H
Exact source Table 6S: # of AKTE2 near gene > 0
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 Human_NCBI_Gene_ID
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Version history 3.1: First introduced

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