Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-22533
PROVIDER: PRJNA128503 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE22533: Breast cancer cells resistant to hormone deprivation maintain an estrogen receptor alpha-dependent, E2F-directed transcriptional program GSE27300: Estrogen-independent genomic ER binding analysis Refer to individual Series
2012-05-14 | E-GEOD-37955 | biostudies-arrayexpress
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells. RAR alpha silenced breast cancer MCF-7 cell lines or control siRNA in the presence of estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen for 12 h. There were three biological replicates for each of the four different groups.
2010-06-16 | E-GEOD-22213 | biostudies-arrayexpress
Project description:Despite the success of the aromatase inhibitors (AIs) in treating estrogen receptor positive breast cancer, 15-20% of patients receiving adjuvant AIs will relapse within 5-10 years of treatment initiation. Long term estrogen deprivation (LTED) of breast cancer cells in culture has been successfully used to mimic AI-induced estrogen depletion to dissect mechanisms of AI resistance. However, we hypothesized that a subset of patients receiving AI therapy may maintain low circulating concentrations of estrogens that influence the development of endocrine resistance. We sought to expand established LTED models to account for these observations. MCF-7 cells were grown in medium with charcoal stripped serum supplemented with defined concentrations of E2 or the estrogenic androgen metabolite 3βAdiol. Cells were selected in the EC10 and EC90 of E2 or 3βAdiol, or estrogen deprived. Estrogen-independence was evaluated during selection by assessing cell growth in the absence or presence of E2 or 3βAdiol. Following >7 months of selection, estrogen-independence developed in estrogen-deprived cells and cells maintained in low concentrations of steroid hormone. Functional analyses demonstrated that estrogen-deprived and low-steroid selected cells developed estrogen-independence via unique mechanisms, independent and dependent of ERα, respectively. Estrogen-independent growth in low-steroid selected cells could be blocked by kinase inhibitors. However, these cells were completely resistant to kinase inhibition in the presence of low steroid hormone concentrations. These data offer a novel perspective on the development of resistance to AI therapy, and may yield novel approaches to treat AI-resistant tumors. MCF-7 cells were selected for >7months in IMEM+10% Charcoal Stripped FBS, supplmented with defined steroid hormone conditions. Following outgrowth of estrogen-independent cells, cell lines were grown in estrogen-free conditions and gene expression analysis was performed to identify drivers of estrogen-independent growth. Cells were assessed in biological triplicates.
2012-03-29 | E-GEOD-33287 | biostudies-arrayexpress
Project description:The nuclear hormone receptor, estrogen receptor-alpha (ERα), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ERα activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ERα colocalization at chromatin binding sites across the genome of breast cancer cells. KEYWORDS: siRNA knock-down, ligand treatment
2011-01-10 | GSE24592 | GEO
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.
2010-06-09 | GSE22213 | GEO
Project description:Estrogen deprivation using aromatase inhibitors is currently the standard of care for patients with estrogen-receptor (ER)-positive breast cancer. Unfortunately, prolonged estrogen deprivation leads to drug resistance (i.e. hormone-independent growth). We therefore used DNA microarray analysis to study the gene expression profiles of wild-type MCF-7 cells (which are sensitive to antihormone therapy) and long-term estrogen deprived MCF-7:5C and MCF-7:2A breast cancer cells (which are resistance to estrogen-deprivation; aromatase inhibitor resistant). Transcriptional profiling of wild-type MCF-7 cells and estrogen deprived MCF-7:5C and MCF-7:2A cells was performed using Affymetrix Human Genome U133 Plus 2.0 Array. Keywords: breast cancer cells, estrogen
2008-03-19 | GSE10879 | GEO
Project description:Hyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer. A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. We used gene expression microarrays to identify genes and pathways that are commonly dysregulated in ER+ cell lines with acquired hormone-independent growth. MCF-7, ZR75-1, MDA-361, and HCC-1428 ER+, estrogen-responsive breast cancer cells were cultured under hormone-depleted conditions (10% DCC-FBS) for several months until sustainable hormone-independent cell populations emerged.
2010-06-15 | GSE19639 | GEO
Project description:Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER) orchestrates a complex molecular circuitry that is not yet fully elucidated. Here we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression. Enrichment analysis of transcription factor (TF) binding and motif occurrence in the proximity of E2 deprivation-mediated differentially methylated and acetylated sites reinforces the importance of AP-1 and FOX proteins, Finally, most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation.
2020-01-01 | GSE132207 | GEO
Project description:Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER) orchestrates a complex molecular circuitry that is not yet fully elucidated. Here we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression. Enrichment analysis of transcription factor (TF) binding and motif occurrence in the proximity of E2 deprivation-mediated differentially methylated and acetylated sites reinforces the importance of AP-1 and FOX proteins, Finally, most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation.
2020-01-01 | GSE132513 | GEO
Project description:Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER) orchestrates a complex molecular circuitry that is not yet fully elucidated. Here we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression. Enrichment analysis of transcription factor (TF) binding and motif occurrence in the proximity of E2 deprivation-mediated differentially methylated and acetylated sites reinforces the importance of AP-1 and FOX proteins, Finally, most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation.
2020-01-01 | GSE132510 | GEO