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Title: Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. [tumor samples RNA-seq]      
dateReleased:
06-01-2016
description:
Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers. ER+/PR+ and ER+/PR-deficient model systems were deprived of steroids by culturing them in phenol red free RPMI 1640 media that is supplemented with 10% charcoal-stripped fetal bovine serum and 1% penicillin/streptomycin. Subsequently, these steroid-deprived models were treated with either vehicle, 10 nM estradiol, 10 nM progestin R5020 or 10 nM of both the hormones and genomics (ChIP-seq and RNA-seq) was performed. ChIP-seq was done after 45 minutes of hormone treatments. For cell models, RNA-seq was done after 12 hours of hormone treatments. Tumor explants were treated with either 24 or 48 hours.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-80365
refinement:
raw
alternateIdentifiers:
80365
keywords:
functional genomics
dateModified:
06-04-2016
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80365/E-GEOD-80365.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80365/E-GEOD-80365.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80365
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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