STANDARD_NAME BHAT_ESR1_TARGETS_VIA_AKT1_DN SYSTEMATIC_NAME M2235 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BHAT_ESR1_TARGETS_VIA_AKT1_DN NAMESPACE Human_NCBI_Gene_ID DESCRIPTION_BRIEF 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]. DESCRIPTION_FULL 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. PMID 18838536 GEOID AUTHORS Bhat-Nakshatri P,Wang G,Appaiah H,Luktuke N,Carroll JS,Geistlinger TR,Brown M,Badve S,Liu Y,Nakshatri H CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 6S: # of AKTE2 near gene > 0 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1001,10057,1021,10826,11099,11179,124359,154313,157638,1628,1903,1907,1942,1948,2059,2099,210,22931,23328,23362,23613,255488,25875,26298,26959,2820,283078,28514,29760,29841,3321,3371,3554,388403,3912,4209,481,51141,51363,5166,54843,5493,55315,55568,55625,55788,55812,57198,57530,57619,5784,5916,5934,598,63027,64067,64764,6645,687,7042,7088,7328,7586,7903,79156,8000,80263,80315,83719,8412,84159,84632,84851,8613,8829,9080,9121,9568,9569,9605,9723,9764 GENE_SYMBOLS CDH3,ABCC5,CDK6,FAXDC2,PTPN21,ZNF277,CDYL2,CFAP206,LRATD2,DBP,S1PR3,EDN2,EFNA1,EFNB2,EPS8,ESR1,ALAD,RAB18,SASH1,PSD3,ZMYND8,RNF144B,LETMD1,EHF,HBP1,GPD2,MKX,DLL1,BLNK,GRHL1,IGSF3,TNC,IL1R1,YPEL2,LAMB1,MEF2D,ATP1B1,INSIG2,CHST15,PDK4,SYTL2,PPL,SLC29A3,GALNT10,ZDHHC7,LMBRD1,SPATA7,ATP8B2,CGN,SHROOM3,PTPN14,RARG,RBL2,BCL2L1,SLC22A23,NPAS3,CREB3L2,SNTB2,KLF9,TGFB2,TLE1,UBE2H,ZKSCAN1,ST8SIA4,PLEKHF1,PSCA,TRIM45,CPEB4,YPEL3,BCAR3,ARID5B,AFAP1L2,TRIM52,PLPP3,NRP1,CLDN9,SLC16A5,GABBR2,GTF2IRD1,VPS9D1,SEMA3E,KIAA0513 FOUNDER_NAMES