Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD002104
PROVIDER: PRJNA282508 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2000680.fastq.gz | Fastqsanger.gz | |||
| SRR2000690.fastq.gz | Fastqsanger.gz | |||
| SRR2000700.fastq.gz | Fastqsanger.gz | |||
| SRR2000710.fastq.gz | Fastqsanger.gz | |||
| SRR2000720.fastq.gz | Fastqsanger.gz |
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Project description:ChIP-seq of ERa and PR in two ER+ breast cancer cell lines treated with and without estrogen and with and without progestins
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Project description:Exploring effect of estrogen and progesterone/progestin treatment on ER and PR binding. Two cell lines, four conditions (Vehicle, E2, Progesterone, E2+Progesterone), three factors (ER, PR, p300), all with three replicates.
2015-05-22 | E-GEOD-68356 | biostudies-arrayexpress
Project description:Progesterone receptors (PR) are co-expressed in over half of estrogen receptor (ER) positive breast cancers and predict positive response to endocrine therapy. PR can directly and globally modify ER action to attenuate tumor growth. However, whether this suppression occurs solely through PR-ER interactions remains unknown. We assessed tumor growth in two highly ER and PR positive breast cancer patient-derived xenografts (PDX) and found that natural and synthetic progestins potently antagonize the mitogenic effects of estrogens. Here we probed the genome-wide mechanisms by which this occurs. Chronic progestin treatment reversed expression of up to half of estrogen up- and downregulated genes at the transcript level. However, fewer than a quarter of ER DNA binding events were altered by progesterone. The PR cistrome showed an interesting bimodal distribution. In the first group, more than half of PR binding sites were co-occupied by ER, with a propensity for both receptors to coordinately gain or lose binding in the presence of progesterone. In the second group, PR, but not ER, was associated with a large fraction of RNA polymerase III (Pol III)-transcribed tRNA genes regardless of hormone treatment. Furthermore, PR formed a physical association with the Pol III holoenzyme. Select tRNAs with colocalization of PR and POLR3A at their promoters were reduced in tumors grown with estrogen plus progestin compared to estrogen alone. These data uncover a mechanism in solid tumors by which PR modulates the bioavailability of translational molecules that are necessary for robust tumor growth, which could indirectly impede ER action.
2017-02-28 | GSE93944 | GEO
Project 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.
2016-06-01 | GSE80367 | GEO
Project 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.
2016-06-01 | GSE80366 | GEO
Project 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.
2016-06-01 | GSE80365 | GEO
Project description:Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors and respond to hormone therapies. Basal-like “triple negative” (TN) cancers lack steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy. Here we show that over half of primary ER+PR+ breast cancers contain an ER–PR–CK5+ “luminobasal” subpopulation exceeding 1% of cells. Starting from ER+PR+ luminal cell lines, we generated novel lines with varying luminal to luminobasal-cell ratios and studied their molecular and biological properties. In luminal disease, luminobasal cells expand in response to antiestrogen or estrogen withdrawal therapies. The phenotype and gene signature of the hormone resistant cells matches that of clinical TN basal-like and claudin-low disease. Luminobasal-cell expansion in response to hormone therapies is regulated by Notch1 signaling and can be blocked by gamma-secretase inhibitors (GSI). Our data establish a previously unrecognized plasticity of ER+PR+ luminal breast cancers that, without genetic manipulation, mobilizes outgrowth of hormone-resistant basal-like disease in response to treatment. This undesirable outcome can be prevented by combining endocrine therapies with Notch inhibition.
2011-12-21 | GSE31870 | GEO
Project description:Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.
2015-03-15 | GSE45643 | GEO
Project description:The prognosis of a patient with Estrogen Receptor (ER) and/or Progesterone Receptor (PR)-positive breast cancer is highly variable. Therefore, we developed a gene-expression based outcome predictor for ER+ and/or PR+ (i.e. Luminal) breast cancer patients using biological properties of the tumors. First, we identified estrogen-regulated genes using the ER+ MCF-7 breast cancer cell line treated with estrogen. The estrogen-induced gene set was then used to hierarchically cluster a training set of 65 ER+ and/or PR+ tumors into 2 group, which showed survival differences (p=0.0004). Next, supervised analyses based upon these two groups was performed and identified 822 genes that optimally defined these two groups, with the poor prognosis Group IIE tumors showing a proliferation signature and high expression of anti-apoptosis genes and the good outcome Group IE showing the high expression of estrogen and GATA3-induced genes. Centroids were created for each group and applied to ER+ and/or PR+ tumors from three published datasets. For all datasets, Kaplan-Meier survival analyses showed a statistically significant difference in Relapse-Free Survival (and Overall) between Group IE and IIE tumors. Multivariate Cox analysis of the largest test dataset also showed that this predictor was adding independent information. This study provides new biological information concerning differences within Luminal/ER+ breast cancers and a means of predicting long term outcomes in ER+ and/or PR+ breast cancer patients. Keywords: other
2005-12-01 | GSE2740 | GEO
Project description:Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors and respond to hormone therapies. Basal-like “triple negative” (TN) cancers lack steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy. Here we show that over half of primary ER+PR+ breast cancers contain an ER–PR–CK5+ “luminobasal” subpopulation exceeding 1% of cells. Starting from ER+PR+ luminal cell lines, we generated novel lines with varying luminal to luminobasal-cell ratios and studied their molecular and biological properties. In luminal disease, luminobasal cells expand in response to antiestrogen or estrogen withdrawal therapies. The phenotype and gene signature of the hormone resistant cells matches that of clinical TN basal-like and claudin-low disease. Luminobasal-cell expansion in response to hormone therapies is regulated by Notch1 signaling and can be blocked by gamma-secretase inhibitors (GSI). Our data establish a previously unrecognized plasticity of ER+PR+ luminal breast cancers that, without genetic manipulation, mobilizes outgrowth of hormone-resistant basal-like disease in response to treatment. This undesirable outcome can be prevented by combining endocrine therapies with Notch inhibition. 24 array samples
2011-12-21 | E-GEOD-31870 | biostudies-arrayexpress