Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA203306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR851926.fastq.gz | Fastqsanger.gz | |||
| SRR851927.fastq.gz | Fastqsanger.gz | |||
| SRR851928.fastq.gz | Fastqsanger.gz | |||
| SRR851929.fastq.gz | Fastqsanger.gz | |||
| SRR851930.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 7 |
Similar Datasets
Project description:LRH-1 governs vital transcriptional programs in endocrine sensitive and resistant breast cancer cells: Expression profiling
| PRJNA237976 | ENA
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor a(ERa)-positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies. ChIP-seq examination of LRH-1 binding sites with specific chromatin marks in MCF7 breast cancer cells.
2014-02-27 | E-GEOD-47027 | biostudies-arrayexpress
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor-α (ERα) positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with signature of poor outcome breast cancer tumors in vivo. Herein report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies.
2014-02-27 | GSE54891 | GEO
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor-α (ERα) positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with signature of poor outcome breast cancer tumors in vivo. Herein report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies. Total RNA was obtained from two biological replicates of breast cancer cells MCF7, LCC2 and LCC9 transduced with LRH-1 shRNA (shLRH-1) or control shRNA (shCTL) lentiviruses.
2014-02-27 | E-GEOD-54891 | biostudies-arrayexpress
Project description:Tumor characteristics are decisive in the determination of treatment strategy for breast cancer patients. Patients with estrogen receptor a(ERa)-positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in anti-estrogen (AE) sensitive and resistant breast cancer cells. We identified genome-wide LRH-1 binding sites using ChIP-seq, uncovering preferential binding to regions distal to transcriptional start sites (TSS). We further characterized these LRH-1 binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1 binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1 depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in AE-sensitive and AE-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies.
2014-02-27 | GSE47027 | GEO
Project description:While ERα+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since in therapy-resistance tumors, ERα is still the main driver, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we describe TRIM24 as a key player of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα-cofactors to facilitate ERα chromatin interactions, and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently-developed PROTAC targeting TRIM24, ERα-driven transcriptional output and growth was blocked, effectively treating not only endocrine-responsive cell lines, but also drug resistant derivates thereof as well as cell line models bearing activating ESR1 point mutations. Finally, using human tumor-derived organoid models, we could show efficacy of TRIM24 PROTAC in the endocrine responsive and resistant setting, with no response in ERα-negative organoids. Overall, our study positions TRIM24 as a central component for integrity and activity of the ERα transcriptional complex, with PROTAC-mediated perturbation of TRIM24 as promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer.
2025-08-01 | PXD046736 | Pride
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 receptor α (ERα) is a nuclear receptor that is the driving transcription factor expressed in the majority of breast cancers. Recent studies have demonstrated that the liver receptor homolog-1 (LRH-1), another nuclear receptor, is ERα-regulated in breast cancer cells. Further, LRH-1 stimulates proliferation and promotes motility and invasion of breast cancer cells. To determine the mechanisms of LRH-1 action in breast cancer cells, we carried out gene expression microarray analysis following siRNA-mediated LRH-1 knockdown. Interestingly, gene ontology (GO) category enrichment analysis of the genes differentially regulated in the presence or absence of LRH-1 identified estrogen responsive genes as the most highly enriched GO categories. To further define LRH-1 target genes, we performed chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) to identify genomic targets of LRH-1. Remarkably, ChIP-seq showed LRH-1 binding at many ERα binding sites. Analysis of select binding sites confirmed regulation of ERα-regulated genes by LRH-1 through binding to estrogen response elements, as exemplified by the TFF1/pS2 gene. Finally, LRH-1 over-expression stimulated ERα recruitment, whilst LRH-1 knockdown reduced ERα recruitment to ERα binding sites. Taken together, our findings establish a key role for LRH-1 in the regulation of ERα target genes in breast cancer cells and identify a mechanism in which co-operative binding of LRH-1 and ERα at estrogen response elements controls the expression of estrogen-responsive genes.
2013-09-01 | GSE47803 | GEO
Project description:The transcriptional activity of the TEAD4 trascription factor requires co-activators. In this study we found that the expression of the TEAD coactivator VGLL1 is repressed in estrogen receptor positive breast cancer but upon resistance to endocrine threapies VGLL1 is expressed to high levels. To elucidate the importance of the coactivator VGLL1 in breast cancer cells resistant to endocrine therapies and to identify the VGLL1 target genes, we performed ChIP-seq for VGLL1 in MCF7 breast cancer cells resistant to fulvestrant (FULVR) and ChiP-seq for TEAD4 in FULVR cells and the isogenic MCF7 cells.
2023-12-05 | GSE216525 | GEO