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GSE36683
Homo sapiens
12 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring potential underlying molecular mechanisms in human MCF7 breast cancer cells. Principal Findings: Gene expression profiling revealed that the expression of approximately 150 genes was influenced by both 17-estradiol (E2) and a hypomethylating agent 5-aza-2-deoxycytidine (DAC). Based on gene ontology (GO), CpG island prediction analysis and previously reported estrogen receptor (ER) binding regions, we selected six genes for further analysis (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2). GO analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis, while CpG island prediction of promoter regions reveals that the promoters of these genes contain at least one CpG island. Using chromatin immunoprecipitation, we show that ER is recruited to CpG islands in promoters, but neither in an E2- nor in a DAC-dependent fashion. DAC treatment reactivates the expression of all selected genes although only the promoters of BTG3 and FHL2 genes are methylated, with E2 treatment showing no effect on the methylation status of these promoters. Conclusions: We identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Publication Title
Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Members of bromodomain and extra-C terminal (BET) domain family and the histone deacetylase (HDAC) enzyme family efficiently regulate the expression of important oncogenes and tumor suppressors. HDACs induce histone hypoacetylation meanwhile BET proteins bind to acetylated lysines on histones to regulate gene transcription. Here we show that the BET inhibitor JQ1 inhibited proliferation and induced apoptosis of both triple negative and estrogen receptor positive breast cancer cells. Consistent with the critical role of histone acetylation in the regulation of gene expression, microarray analysis revealed broad transcriptional changes after JQ1 or HDAC inhibitor treatment. By examining the molecular pathways affected by the epigenetic inhibitors we found that both BET and HDAC inhibitors are suppressing similar genes that were involved in cell cycle regulation. Combining JQ1 with HDAC inhibitors, we found that the combination significantly decreased cell viability. This effect was partly mediated by the more efficient suppression of genes essential for cell-cycle progression. Furthermore, we detected a dramatic increase in the expression of several members of the USP17 family of deubiquitinating enzymes in response to the single agent treatment, which further increased by the combination treatment. Since constitutive expression of USP17 has been reported to block the Ras/MAPK pathway, our data also suggest that the blockade of the Ras/MAPK pathway might also be involved in the synergistic effect of the combination treatment. In conclusion, this study suggests that co-treatment with BET inhibitors and HDAC inhibitors could be an effective treatment regime in future breast cancer therapy.
Publication Title
Induction of USP17 by combining BET and HDAC inhibitors in breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina Genome Analyzer, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AP-1 Is a Key Regulator of Proinflammatory Cytokine TNFα-mediated Triple-negative Breast Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina Genome Analyzer
Description
Triple-negative breast cancer (TNBC) represents a highly aggressive form of breast cancer with limited treatment options. Proinflammatory cytokines such as TNFalpha can facilitate tumor progression and metastasis. However, our knowledge of the molecular mechanisms underlying TNBC progression mediated by inflammation is still limited. Here, we define the AP-1 transcription factor c-Jun cistrome, which is comprised of 13800 binding sites responsive to TNFalpha-induced signaling in TNBC cells. In addition, we show that c-Jun regulates nearly a third of the TNFalpha-elicited transcriptome. Expression of the c-Jun-regulated pro-invasion gene program is strongly associated with clinical outcomes in TNBCs. Mechanistically, we demonstrate that c-Jun drives TNFalpha-mediated TNBC tumorigenicity by transcriptional regulation of Ninj1. As exemplified by the c-Jun bound CXC chemokine genes clustered on chromosome 4, we demonstrate that NF-kB might be a pioneer factor and is required for the regulation of TNFalpha-inducible inflammatory genes, whereas c-Jun has little effect. Together, our results uncover AP-1 as an important determinant for inflammation-induced cancer progression, rather than inflammatory response.
Publication Title
AP-1 Is a Key Regulator of Proinflammatory Cytokine TNFα-mediated Triple-negative Breast Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina HiSeq 2000
Description
To investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis.
Publication Title
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. Methods. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. Findings. There were no significant differences in gene expression for any transcript. Conclusions. Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.
Publication Title
Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples