HMGB2 in endocrine resistant breast cancer
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR338502.fastq.gz | Fastqsanger.gz | |||
| ERR338503.fastq.gz | Fastqsanger.gz | |||
| ERR338504.fastq.gz | Fastqsanger.gz | |||
| ERR338505.fastq.gz | Fastqsanger.gz | |||
| ERR338506.fastq.gz | Fastqsanger.gz |
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Project description:HMGB2 and ER ChIPseq was investigated in the MCF-7 endocrine sensitive and LY2 endocrine resistant cell lines upon treatment with Tamoxifen.
2014-09-18 | E-MTAB-1865 | biostudies-arrayexpress
Project description:RNA sequencing of endocrine resistant breast cancer
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Project description:*** This submission includes RNA data, with DNA files available under a different accession number*** Purpose: Endocrine therapy resistance remains the greatest challenge for treating hormone receptor positive breast cancer patients. We aim to identify molecular mechanisms underlying endocrine therapy resistance through in-depth genomic analysis of patient samples. Experimental Design: We collected tumors from 35 estrogen receptor positive breast cancer patients receiving endocrine therapy, of which 3 patients had intrinsic resistance and 19 patients developed acquired resistance. For each patient, multiple tumor specimens were collected during the course of treatment. We performed DNA whole exome sequencing and RNA sequencing on all tumor samples. DNA mutations, copy number alterations and RNA gene expression data were analyzed through supervised analyses comparing paired sensitive and resistant tumor samples to identify molecular features related to endocrine therapy resistance. Results: We identified mutations enriched in resistant tumors including ESR1 and GATA3. ESR1 D538G variant confers endocrine therapy resistance while E380Q variant confers hypersensitivity. We demonstrate that resistant tumors had distinct gene expression profiles and elevated signaling pathways including ER, HER2, GATA3, AKT, RAS and p63 signaling. Integrated analysis for individual patient highlighted the heterogeneity of endocrine therapy resistance mechanisms. Conclusions: Our results suggest that mechanisms underlying endocrine therapy resistance are highly heterogeneous with diverse changes in genomic and transcriptomic levels.
2022-09-01 | E-MTAB-9917 | biostudies-arrayexpress
Project description:The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid independent tumour. The p160 steroid coactivator protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors drives this tumour adaptability. Here, using discovery studies we identify ADAM22, a non-protease member of the ADAMs family, as a direct target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression. ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer. 14 samples representing 4 conditions were analysed. Samples were transfected with either a siRNA targetting SRC1 or a control scrambled siRNA. Samples were subject to tamoxifen treatment or untreated.
2012-01-11 | E-GEOD-28645 | biostudies-arrayexpress
Project description:The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid independent tumour. The p160 steroid coactivator protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors drives this tumour adaptability. Here, using discovery studies we identify ADAM22, a non-protease member of the ADAMs family, as a direct target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression. ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer.
2012-01-11 | GSE28645 | GEO
Project description:Around two thirds of breast tumors are characterized by the expression of estrogen receptor α and are therapeutically treated by blocking estrogen signaling. First line endocrine therapeutics are Tamoxifen which displaces estrogen form its receptor preventing receptor activation and aromatase inhibitors which prevent the formation of estrogen and thereby hormone-deprive the tumors. Therapy resistance remains a major clinical problem, especially for patients with late-stage diagnoses. Tumor heterogeneity may promote therapy resistance either through the selection of pre-existing rare clones or by providing a repertoire of cells that may develop resistance over time. In order to study endocrine therapy resistance on a clonal level, we have developed barcoded (allowing the tracking of single cells) endocrine therapy sensitive and resistant breast cancer cell lines. From these complex cell pools, multiple single cells characterized by a specific barcode were isolated and grown out. We then subjected the clones to phosphoproteomics measurement by Mass spectrometry. Based on their phosphorylation pattern, the kinase activity profiles of endocrine therapy resistant clones were determined to identify differentially activated kinases with implications in therapy resistance.
2024-01-26 | PXD040478 | Pride
Project description:Around 35% of Estrogen Receptor (ER) positive patients develop resistance and relapse, highlighting the need to further understand the mechanisms underpinning endocrine resistance in breast cancer. Here, we study 3-dimensional (3D) epigenome remodelling in endocrine resistant breast cancer cells. We show that chromatin interactions both within and between topologically associating domains (TADs) frequently change in resistant breast cancer cells and that alterations in active (A-type) and inactive (B-type) chromosomal compartments are associated with decreased ER binding and atypical interactions and gene expression. Finally, we identify differentially interacting ER-bound regions that preferentially connect active enhancers and promoters associated with altered expression of ER-regulated genes. Importantly, interactions specifically associated with endocrine resistance, often occur coincidently with hypermethylation of ER binding. Our results demonstrate that 3D epigenome remodelling is a key mechanism of endocrine resistance that consists of differential chromatin interactions and aberrant DNA methylation at ER-regulated enhancer regions.
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Project description:To explore the mechanism of endocrine resistance development in estrogen receptor positive breast cancer, transcriptome analysis of MCF-7 and its endocrine resistant derivatives, including tamoxifen resistant (TAMR) sub-lines and long-term estrogen deprivation (LTED) sub-lines, were performed using microarray.
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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.
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Project description:The majority of breast cancers (BCs) harboring estrogen receptor (ER) have shown endocrine resistance. Our previous study has demonstrated that ferredoxin reductase (FDXR) promotes mitochondrial function and ER+ breast tumorigenesis. Here, integrative analyses of targeted metabolomics assay and gene expression profiling show that FDXR potentiates fatty acid oxidation (FAO) through positive regulation of carnitine palmitoyltransferase 1A (CPT1A) expression. Treatment with ER antagonist (tamoxifen) or degrader (fulvestrant) leads to increased expression of FDXR and CPT1A. In line with this finding, we find that FDXR-CPT1A-FAO axis is required for primary and endocrine resistant breast cancer cell growth. Therapeutically,combining endocrine therapy with FAO inhibitor synergistically reduces primary and endocrine resistant breast cancer cell growth, thus providing a potential combinatory treatment for ER+ breast cancer. We used microarrays to be able to elucidate to some extent the gene regulatory mechanisms of FDXR regulating breast cancer metabolism.
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