Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-22533
PROVIDER: PRJNA167152 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR100284.fastq.gz | Fastqsanger.gz | |||
| SRR100285.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
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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:The estrogen receptor alpha (ERa) drives the growth of two-thirds of all breast cancers. Endocrine therapy impinges on estrogen-induced ERa activation to block tumor growth. However, half of ERa-positive breast cancers are tolerant or acquire endocrine therapy resistance. Here we demonstrate that breast cancer cells undergo genome-wide reprogramming of their chromatin landscape, defined by epigenomic maps and chromatin openness, as they acquire resistance to endocrine therapy. This reveals a role for the Notch pathway while excluding classical ERa signaling. In agreement, blocking Notch signaling, using gamma-secretase inhibitors, or targeting its downstream gene PBX1 abrogates growth of endocrine therapy-resistant breast cancer cells. Moreover Notch signaling through PBX1 directs a transcriptional program predictive of tumor outcome and endocrine therapy response.
2013-05-01 | GSE37323 | GEO
Project description:The estrogen receptor alpha (ERa) drives the growth of two-thirds of all breast cancers. Endocrine therapy impinges on estrogen-induced ERa activation to block tumor growth. However, half of ERa-positive breast cancers are tolerant or acquire endocrine therapy resistance. Here we demonstrate that breast cancer cells undergo genome-wide reprogramming of their chromatin landscape, defined by epigenomic maps and chromatin openness, as they acquire resistance to endocrine therapy. This reveals a role for the Notch pathway while excluding classical ERa signaling. In agreement, blocking Notch signaling, using gamma-secretase inhibitors, or targeting its downstream gene PBX1 abrogates growth of endocrine therapy-resistant breast cancer cells. Moreover Notch signaling through PBX1 directs a transcriptional program predictive of tumor outcome and endocrine therapy response. Comparing histone modifications (H3K4me2 and H3K36me3), chromatin openness (FAIRE) and PBX1 binding between endocrine therapy sensitive MCF7 and resistant MCF7-LTED cells.
2013-05-01 | E-GEOD-37323 | biostudies-arrayexpress
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:Aromatase inhibitors are first-line postmenopausal agents for estrogen receptor alpha (ERa)-positive breast cancer. However, there is considerable response heterogeneity and women frequently relapse. Estrogen deprivation does not completely arrest ERa activity, and transactivation of the unliganded receptor may continue through cross-talk with growth factor pathways. In contrast with aromatase inhibitors, the selective ER downregulator fulvestrant also abrogates ligand-independent ERa activity. The benefit of fulvestrant as an alternative, combination, or sequential therapy to aromatase inhibitor has been reported, but molecular mechanisms underpinning its relative efficacy remain unclear and biomarkers for patient selection are lacking. This study demonstrates, for the first time, that the overall transcriptional response to fulvestrant is of greater magnitude than estrogen deprivation, consistent with its clinical efficacy and more complete blockade of estrogenic signaling. Using a robust integrative approach, we identify a subset of genes differentially affected by fulvestrant that comprises distinct biologic networks, correlates with antiproliferative response, and has potential utility as predictive biomarkers for fulvestrant. Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 38) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance. --------------------------------- This represents the data for fulvestrant only
2015-08-07 | E-GEOD-71791 | biostudies-arrayexpress
Project description:Estrogen Receptor alpha (ERa) is the main driver of luminal breast cancer development and progression, and represents the main drug target in patient care. ERa chromatin binding has been extensively studied in breast cancer cell lines and a number of human tumors, often focused on differential binding patterns between groups or conditions. However, little is known about the inter-tumor heterogeneity of ERa chromatin action. Here, we use a large set of ERa ChIP-seq data from 70 ERa+ breast cancers (40 women & 30 men) to explore general inter-patient heterogeneity in ERa DNA binding in breast cancers. We found a total universe of 84,565 and 101,653 ERa sites in females and males respectively, with merely 1.2% and 5% of sites shared in at least half of the tumors analyzed, reflecting a high level of inter-patient heterogeneity. This heterogeneity was found to be most variable at putative enhancers as opposed to promoter regions, potentially reflecting a level of functional redundancy in enhancer action. Interestingly, commonly shared ERa sites showed the highest estrogen-driven enhancer activity, as determined using a massive parallel reporter assay, and were most-engaged in long-range chromatin interactions. In addition, the most-commonly shared ERa-occupied enhancers were found enriched for breast cancer risk SNP loci. We experimentally illustrate such SNVs can impact chromatin binding potential for ERa and its pioneer factor FOXA1. Finally, in the TCGA breast cancer cohort, we could confirm these variations to associate with differences in expression for the target gene. Cumulatively, our data reveal a natural hierarchy of ERa-chromatin interactions in breast cancers within a highly heterogeneous inter-tumor ERa landscape, with the most-common shared regions being most active and affected by germline functional risk SNPs for breast cancer development.
2024-05-22 | PXD045526 | Pride
Project description:Aromatase inhibitors are first-line postmenopausal agents for estrogen receptor alpha (ERa)-positive breast cancer. However, there is considerable response heterogeneity and women frequently relapse. Estrogen deprivation does not completely arrest ERa activity, and transactivation of the unliganded receptor may continue through cross-talk with growth factor pathways. In contrast with aromatase inhibitors, the selective ER downregulator fulvestrant also abrogates ligand-independent ERa activity. The benefit of fulvestrant as an alternative, combination, or sequential therapy to aromatase inhibitor has been reported, but molecular mechanisms underpinning its relative efficacy remain unclear and biomarkers for patient selection are lacking. This study demonstrates, for the first time, that the overall transcriptional response to fulvestrant is of greater magnitude than estrogen deprivation, consistent with its clinical efficacy and more complete blockade of estrogenic signaling. Using a robust integrative approach, we identify a subset of genes differentially affected by fulvestrant that comprises distinct biologic networks, correlates with antiproliferative response, and has potential utility as predictive biomarkers for fulvestrant.
2015-08-07 | GSE71791 | GEO
Project description:ESRRA (Estrogen-Related Receptor Alpha) is an orphan nuclear receptor that plays a pivotal role in regulating cellular metabolism, mitochondrial biogenesis, and energy homeostasis through gene transcriptional control. It has been implicated in various physiological processes and diseases, including cancer. However, the transcriptional programs it regulates and the underlying molecular mechanisms are yet to be comprehensively understood. Here, we demonstrated that ESRRA serves as a central regulator in orchestrating the transcriptional activation of ERa-occupied super enhancers (ERSEs) and cognate ERa-target genes. Meanwhile, it downregulates the expression of cytosolic RNA sensors RIG1 and MDA5 to inhibit type I interferon (IFN) and type I IFN-stimulated genes (ISGs). In terms of mechanism, ESRRA is recruited to ERSEs together with ERain response to estrogen, and their binding with ESREs are regulated in a mutual-dependent manner. However, ESRRA directly binds to the promoter regions of RIG1 and MDA5 to suppress their expression. Consistent with these findings, pharmacological inhibition of ESRRA with its inverse agonist XCT790 inhibits estrogen/ERa-induced gene transcription, and enhances the type I IFN pathway and antitumor immunity to suppress breast cancer cell growth both in vitro and in vivo. Co-treatment with XCT790 and endocrine therapy drugs including ERa antagonist Tamoxifen or degrader Fulvestrant exhibited synergistic effects. Furthermore, combination treatment with XCT790 and tamoxifen re-sensitized Tamoxifen-resistant (TamR) ERa-positive breast cancer cells to Tamoxifen treatment. In summary, our findings unveiled that ESRRA is a pivotal regulator of ERSEs and estrogen/ERa-target gene activation, as well as the type I IFN signaling pathway, offering a promising therapeutic avenue for treating ERa-positive breast cancer in the clinic.
2026-02-13 | GSE267725 | GEO
Project description:ESRRA (Estrogen-Related Receptor Alpha) is an orphan nuclear receptor that plays a pivotal role in regulating cellular metabolism, mitochondrial biogenesis, and energy homeostasis through gene transcriptional control. It has been implicated in various physiological processes and diseases, including cancer. However, the transcriptional programs it regulates and the underlying molecular mechanisms are yet to be comprehensively understood. Here, we demonstrated that ESRRA serves as a central regulator in orchestrating the transcriptional activation of ERa-occupied super enhancers (ERSEs) and cognate ERa-target genes. Meanwhile, it downregulates the expression of cytosolic RNA sensors RIG1 and MDA5 to inhibit type I interferon (IFN) and type I IFN-stimulated genes (ISGs). In terms of mechanism, ESRRA is recruited to ERSEs together with ERain response to estrogen, and their binding with ESREs are regulated in a mutual-dependent manner. However, ESRRA directly binds to the promoter regions of RIG1 and MDA5 to suppress their expression. Consistent with these findings, pharmacological inhibition of ESRRA with its inverse agonist XCT790 inhibits estrogen/ERa-induced gene transcription, and enhances the type I IFN pathway and antitumor immunity to suppress breast cancer cell growth both in vitro and in vivo. Co-treatment with XCT790 and endocrine therapy drugs including ERa antagonist Tamoxifen or degrader Fulvestrant exhibited synergistic effects. Furthermore, combination treatment with XCT790 and tamoxifen re-sensitized Tamoxifen-resistant (TamR) ERa-positive breast cancer cells to Tamoxifen treatment. In summary, our findings unveiled that ESRRA is a pivotal regulator of ERSEs and estrogen/ERa-target gene activation, as well as the type I IFN signaling pathway, offering a promising therapeutic avenue for treating ERa-positive breast cancer in the clinic.
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