|
| Status |
Public on Jun 01, 2016 |
| Title |
Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Greene G, Singhal H |
| Citation(s) |
27386569 |
| |
| Submission date |
Apr 18, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Hari Singhal |
| E-mail(s) |
hari_singhal@dfci.harvard.edu
|
| Organization name |
University of Chicago
|
| Department |
Ben May Department for Cancer Research
|
| Lab |
Geoffrey L Greene
|
| Street address |
929 E 57th St
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (26)
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| This SubSeries is part of SuperSeries: |
| GSE80098 |
Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. |
|
| Relations |
| BioProject |
PRJNA318944 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80367_T47D_ER_E2+R5020_WC8_Vehicle_subtracted_.bed.gz |
208.5 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_ER_E2_WC4_Vehicle_subtracted_.bed.gz |
52.8 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_ER_R5020_WC6_Vehicle_subtracted_.bed.gz |
58.4 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR-deficient_ER_E2+R5020_YC4_Vehicle_subtracted_.bed.gz |
72.0 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR-deficient_ER_E2_YC2_Vehicle_subtracted_.bed.gz |
98.4 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR-deficient_ER_R5020_YC3_Vehicle_subtracted_.bed.gz |
97.1 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR_E2+R5020_WC7_Vehicle_subtracted_.bed.gz |
130.8 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR_E2_WC3_Vehicle_subtracted_.bed.gz |
85.9 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_PR_R5020_WC5_Vehicle_subtracted_.bed.gz |
66.3 Kb |
(ftp)(http) |
BED |
| GSE80367_T47D_reChIP_ERPRComplexes_E2+R5020_RC3_subtracted_Veh_and_IgG_.bed.gz |
110.1 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data provided as supplementary file |
| Processed data are available on Series record |
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