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GSE45643
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor- (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.
Publication Title
Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
Publication Title
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
analyzed changes in cytokine/chemokine production and gene expression levels in, human peripheral blood mononuclear cells upon teratment with 15M,2,4-benzenetriol
Publication Title
Identification of human cell responses to benzene and benzene metabolites.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2000
Description
Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. Overall design: We collected separately cortical gray (GM) and subcortical white matter (WM) from 6 adult human subjects without neurological disease and extracted total RNA processed by the RNA-Seq approach.
Publication Title
Deciphering H3K4me3 broad domains associated with gene-regulatory networks and conserved epigenomic landscapes in the human brain.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore, we investigated whole genome differential expression in the preconditioned rat brain.
Publication Title
Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Foxp3-dependent programme of regulatory T-cell differentiation.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This data set is comprised of all peripheral (pooled lymph nodes and spleen) T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R cells; T-25, T-FN and T-R cells from mice treated with IL-2; and T-R cells transduced with empty, PDE3B-expressing or PDE3B(H801A)-expressing retroviral vectors (after transfer into recipient mice).
Publication Title
Foxp3-dependent programme of regulatory T-cell differentiation.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This data set is comprised of all thymic T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R thymocytes.
Publication Title
Foxp3-dependent programme of regulatory T-cell differentiation.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TIMP-2 is an endogenous angiogenesis inhibitor, i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis.
Publication Title
TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Increasing evidence indicates stem cell transplantation may be an effective stroke treatment but little is known about the direct impact of transplanted cells on injured brain tissue. We investigated the effects of lineage negative murine hematopoietic stem/progenitor cells (HSPCs) on the cerebral microcirculation following ischemia-reperfusion injury (I/RI). Following subsequent evaluation of the mRNA transcriptome of the explanted HSPCs, we assessed whether metallothionein (MT)-1, (increased in explanted HSPCs from I/R mice) administration was able to evoke similar neuro-protection following cerebral I/RI. Methods and Results: Murine HSPCs administered intravenously 24 hours (h) post cerebral I/R were selectively recruited to the brain of I/RI mice. Mice treated with HSPCs displayed decreased disease severity for up to 2-weeks post cerebral I/R, as evidenced by decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation and elevated plasma levels of anti-inflammatory interleukin-10. Using confocal intravital microscopy, we found that transplanted cells had emigrated into the brain parenchyma and that RNA-seq analysis of explanted HSPCs indicated significantly increased levels of metallothionein transcripts, in particular MT-1. We further determined that treatment of mice with MT-1 significantly reduced neurological score and IV. Conclusions: These studies provide further evidence for HSPCs as a promising therapeutic strategy in promoting repair following cerebral I/RI, potentially via a MT-1 mechanism. Overall design: Murine HSPCs were administered into mice with I/RI intravenously 24 hours post cerebral I/R and selectively recruited to the brain. RNA profiles of explanted HSPCs were determined by RNA sequencing.
Publication Title
Metallothionein I as a direct link between therapeutic hematopoietic stem/progenitor cells and cerebral protection in stroke.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples