Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA237976 | ENA |
REPOSITORIES: ENA
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Project description:LRH-1 governs vital transcriptional programs in endocrine sensitive and resistant breast cancer cells: LRH-1 ChIP-seq
| PRJNA203306 | 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. 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-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 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: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:Expression of estrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy as part of their adjuvant care, but does not guarantee patient response. However, the molecular factors that define endocrine response in ESR1-positive breast cancer patients remain poorly understood. Here, we characterize the DNA methylome of endocrine sensitivity and demonstrate the potential impact of differential DNA methylation on endocrine response in breast cancer. We show that DNA hypermethylation occurs predominantly at estrogen-responsive enhancers and is associated with reduced ESR1 binding and decreased gene expression of key regulators of ESR1-activity; thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. Conversely, we delineate that ESR1-responsive enhancer hypomethylation is critical in transition from normal mammary epithelial cells to endocrine responsive ESR1-positive cancer. Cumulatively these novel insights highlight the potential of ESR1-responsive enhancer methylation to both predict ESR1-positive disease and stratify ESR1-positive breast cancer patients as responders to endocrine therapy. Methylation profiling with Illumina's HumanMethylation450K array was performed on ESR1-positive hormone sensitive MCF7 cells, and three different well characterised endocrine resistant MCF7-derived cell lines; tamoxifen-resistant (TAMR), fulvestrant-resistant (FASR) and estrogen deprivation resistant (MCF7X) cells. For each cell line two biological replicates were profiled bringing the number of samples to eight.
2015-07-01 | E-GEOD-69118 | biostudies-arrayexpress
Project description:Advanced breast cancer is characterised by enhanced tumour adaptability to therapeutic pressure and the metastatic microenvironment. Transcriptome differences in three ER positive (ER+) cell models are uncovered through this RNA-seq analysis of MCF7 (endocrine sensitive), LY2 (endocrine resistant) and T347 (derived from an ER-positive, treatment resistant brain metastatic patient tumour) cells.
2023-05-16 | GSE176534 | GEO
Project description:Forkhead box A1 (FOXA1) is a pioneer factor that facilitates chromatin binding and function of lineage-specific and oncogenic transcription factors. Here, we have demonstrated that FOXA1 overexpression in estrogen receptor-positive breast cancer cells drives genome-wide enhancer reprogramming to activate pro-metastatic transcriptional programs. We have identified the hypoxia-inducible transcription factor HIF-2α as the top FOXA1-engaged super-enhancer target induced by FOXA1 overexpression, activating pro-metastatic gene signatures associated with poor breast cancer outcome. Using two different siRNA sequences, we identified 917 and 1,107 genes commonly down- and up-regulated (FDR < 0.05), respectively, upon HIF-2α knockdown in tamoxifen-resistant MCF7L cells. The enriched GO terms of the down-regulated genes were predominantly linked to tumor metastatic traits. GSEA showed that this HIF-2α-dependent gene set was significantly enriched in the transcriptomes of the TCGA ER+ breast tumors expressing high HIF-2α, but not high HIF-1α. We show the selective efficacy of a HIF-2α antagonist (PT2385), currently in clinical trial for renal cell carcinoma, in repressing migration and clonogenicity of endocrine-resistant breast cancer cells expressing high FOXA1. Our study suggests that targeting HIF-2α is a new approach blocking the aberrant transcriptional programs under high FOXA1-induced enhancer reprogramming in treating endocrine-resistant and metastatic breast cancer.
2019-12-18 | GSE124655 | GEO