Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA99973 | ENA |
REPOSITORIES: ENA
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Project description:This study tried to determine whether exposure of breast stem/progenitor cells to estrogen disrupts the epigenome of progeny epithelial cells. DNA methylation profiles were compared between control and pre-exposed epithelial cells using a genome-wide detection method called MeDIP-chip. Keywords: MeDIP-chip
2007-12-01 | GSE7844 | GEO
Project description:This study tried to determine whether exposure of breast stem/progenitor cells to estrogen disrupts the epigenome of progeny epithelial cells. DNA methylation profiles were compared between control and pre-exposed epithelial cells using a genome-wide detection method called MeDIP-chip. Keywords: MeDIP-chip Breast stem/progenitor cells were continuously exposed to 17beta-estradiol (E2, 70 nM) or DMSO (vehicle control) for two weeks and then placed on 2-dimensional collagen substratum for 2-3 weeks for epithelial cell differentiation. DNA from control and pre-exposed cells were extracted and MeDIP ssays were performed using antibodies against 5-methylcytosine. The immunoprecipitated and input DNA were used to probe the Agilent human CpG island microarray. Dye-swap experiments were also performed.
2007-11-30 | E-GEOD-7844 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of normal human epithelial tissues of breast colon lung and endometrial origin, WBC and sperm to identify breast-specific methylated gene promoter loci. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Breast tissues were pre-enriched for organoids and other epithelial tissues were carefully selected by the pathologist.
2014-01-14 | GSE54025 | GEO
Project description:The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. To comprehensively characterize the influence of estrogen signaling on LRES, we analyzed transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This ?omics? approach uncovered 11 large repressive zones (range: 0.35~5.98 megabases), including a 14-gene cluster located on 16p11.2. In normal cells, estrogen signaling induced transient formation of multiple DNA loops in the 16p11.2 region by bringing 14 distant loci to focal ESR1-docking sites for coordinate repression. However, the plasticity of this free DNA movement was reduced in breast cancer cells. Together with the acquisition of DNA methylation and repressive chromatin modifications at the 16p11.2 loci, an inflexible DNA scaffold may be a novel determinant used by breast cancer cells to reinforce estrogen-mediated repression. ChIP-seq: E2-preexposed or DMSO-preexposed mammosphere-derived epithelial cells (MDECs); MCF-7 cells with 4hr of DMSO or E2 stimulation. MeDIP-chip: Methylated DNA from MCF7 cells was immunoprecipitated by the antibody against 5-methyl cytidine. The immunoprecipitated methylated DNA fragments were processed by the NimbleGen Methylation Microarray Service. Methylation analysis was performed on the NimbleGen Two-Array HG18 Promoter Set. mRNA profiling by array: Four sets of total RNA samples from the mammary gland of each 50-day-old rat with prepubertal exposure of BPA. Each sample set includes one BPA-exposed and one sesame oil-exposed rat RNA.
2010-04-29 | E-GEOD-21068 | 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: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.
2015-07-01 | GSE69118 | GEO
Project description:Genome wide DNA methylation profiling of normal human epithelial tissues of breast colon lung and endometrial origin, WBC and sperm to identify breast-specific methylated gene promoter loci. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Breast tissues were pre-enriched for organoids and other epithelial tissues were carefully selected by the pathologist. Bisulphite converted DNA from the 23 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. Two arrays of 12 and samples each were run separately. Each array included a control of human sperm DNA treated with SssI CpG methylase and human sperm DNA not treated (one sample did not pass QC and was dicarded ) .
2014-01-14 | E-GEOD-54025 | biostudies-arrayexpress
Project description:Divergent estrogen receptor (ER) and HER2 status with breast cancer disease progression has important consequences for clinical management and long-term survival. Molecular subtype expression is dynamic and influenced by therapeutic intervention and the metastatic environment. HER2 status, ER expression levels and global DNA methylation was assessed in pre-treatment biopsies, in post-treatment samples in patients with residual disease and, where relevant, in metastatic tumour samples. Mapping of the methylation landscape revealed global gains in hypomethylation following treatment (n=7 matched tumours, 16 samples) in contrast to hypermethylation on metastasis (n=5 matched tumours, 14 samples). Differential methylation of key signalling pathways, including estrogen response, epithelial to mesenchymal transition and PI3K/AKT/mTOR, is conserved between post-treatment and metastasis. However, where core pathway genes were hypomethylated following treatment, there was a shift to hypermethylation on metastasis, facilitating alterations in the tumour phenotype. This study unlocks DNA methylation as a key process in breast cancer progression providing vital insights into the effects of targeted HER2 treatment. This work provides a clear rationale to develop combined HER2 inhibitor and endocrine therapeutic strategies to enhance long-term survival in HER2 positive patients.
2024-12-16 | GSE283272 | GEO
Project description:DNA methylation changes during immortalization of breast cells. The aim of the study was to determine whether differential epigentic state of TERT gene is involved in immortalization of breast cells. comparison of Pre-Stasis, Post-Selection, and immortal cells
2013-07-03 | E-GEOD-48447 | biostudies-arrayexpress
Project description:Limited knowledge of the changes in estrogen receptor (ER) signaling during the transformation of the normal mammary gland to breast cancer hinders the development of effective prevention and treatment strategies. Differences in estrogen signaling between normal human primary breast epithelial cells and primary breast tumors obtained immediately following surgical excision were explored. Transcriptional profiling of normal ER+ mature luminal mammary epithelial cells and ER+ breast tumors revealed significant difference in the response to estrogen stimulation. Consistent with these differences in gene expression, the normal and tumor ER cistromes were distinct and sufficient to segregate normal breast tissues from breast tumors. The selective enrichment of the DNA binding motif GRHL2 in the breast cancer-specific ER cistrome suggests that it may play a role in the differential function of ER in breast cancer. Depletion of GRHL2 resulted in altered ER binding and differential transcriptional responses to estrogen stimulation. Furthermore, GRHL2 was demonstrated to be essential for estrogen-stimulated proliferation of ER+ breast cancer cells. DLC1 was also identified as an estrogen-induced tumor suppressor in the normal mammary gland with decreased expression in breast cancer. In clinical cohorts, loss of DLC1 and gain of GRHL2 expression are associated with breast cancer and are independently predictive for worse survival. This study suggests that normal ER signaling is lost and tumor-specific ER signaling is gained during breast tumorigenesis. Unraveling these changes in ER signaling during breast cancer progression should aid the development of more effective prevention strategies and targeted therapeutics. SIGNIFICANCE STATEMENT: Abnormal estrogen receptor (ER) signaling drives the majority of breast cancers and is targeted by endocrine therapies. However, in normal breast tissue, ER signaling has been demonstrated to promote benign functions such as development and differentiation. Using genomic techniques to characterize ER function in normal breast and breast tumors, this study reveals differential patterns of ER signaling, suggesting that normal ER signaling is lost and tumorigenic ER signaling gained during breast tumor formation. Better understanding of this process can aid the development of improved breast cancer prevention strategies and therapies.
2019-05-27 | GSE99680 | GEO