STANDARD_NAME	WILLIAMS_ESR2_TARGETS_UP
SYSTEMATIC_NAME	M18326
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WILLIAMS_ESR2_TARGETS_UP
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes uniquely up-regulated in T47D cells (breast cancer) by induction of ESR2 [GeneID=2100] expression in the Tet-Off system.
DESCRIPTION_FULL	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.
PMID	17700529
GEOID	E-MEXP-969
AUTHORS	Williams C,Edvardsson K,Lewandowski SA,Ström A,Gustafsson JA
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ALG14,ANXA9,APOD,CYB5R3,DKFZp434C212,DKFZp761D0211,GSTT2,HIG1,HMGCL,JJAZ1,KCTD11,KIF21A,LDHC,LOC114990,LOC283932,LRRC15,NDRG3,NRIP3,OXR1,P2RY2,PIGK,PTK9L,QSCN6,RG9MTD2,SEPT9,STAU,STK3,UGT1A9,UQCRFS1
GENE_SYMBOLS	ALG14,ANXA9,APOD,CYB5R3,GAPVD1,FAM234A,GSTT2,HIGD1A,HMGCL,SUZ12,KCTD11,KIF21A,LDHC,VASN,FBXL19-AS1,LRRC15,NDRG3,NRIP3,OXR1,P2RY2,PIGK,TWF2,QSOX1,TRMT10A,SEPTIN9,STAU1,STK3,UGT1A9,UQCRFS1
FOUNDER_NAMES