Exogenous 17-estradiol (E2) accelerates the progression of ovarian cancer in the transgenic tgCAG-LS-TAg mouse model of the disease. We hypothesized that E2 has direct effects on ovarian cancer cells and this study was designed to determine the molecular mechanisms by which E2 accelerates ovarian tumour progression. Mouse ovarian cancer ascites (MASE2) cell lines were derived from tgCAG-LS-TAg mice. Following intraperitoneal engraftment of MASE2 into SCID mice, exogenous E2 significantly decreased the survival time and increased the tumour burden.
17β-estradiol upregulates GREB1 and accelerates ovarian tumor progression in vivo.
No sample metadata fields
View SamplesPre-LVAD and explanted ischemic and nonischemic cardiomyopathy and nonfailing hearts all normalized with RMA
Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure.
No sample metadata fields
View SamplesStroke is a multiphasic progress characterized by neuron damage due to hypoxia followed by secondary damage from the subsequent inflammatory immune response. Infiltrating myeloid cells induce cerebral damage through pro-inflammatory cytokines, chemokines, proteases and generation of reactive oxygen species (ROS).
Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity.
Sex, Specimen part
View SamplesNSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimers disease (AD) at preclinical stages in cognitively normal aging populations. We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action.
Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer's disease model mice.
Age, Specimen part, Treatment
View SamplesWe examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Specimen part
View SamplesCell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Specimen part, Cell line
View SamplesSecreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1 down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1 on expression of genes encoding secreted proteins. Interestingly, PGC-1 requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1 modulates the secretome of mouse embryonic fibroblasts (MEFs).
Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.
Specimen part
View SamplesSlow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a non-cycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA-sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses – the p53 transcriptional response and the integrated stress response – are the most salient causes of spontaneous entry into the slow-cycling state. Overall design: mRNA profiling of spontaneously quiescent human cells and cells forced into quiescence by four different methods
Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.
Cell line, Subject
View SamplesHuman embryonic stem cells (hESCs) have the unique property of immortality, ability to infinitely self-renew and survive in vitro. In contrast to tumor-deribed cells, their immortality are free from any genomic abberations. Instead, they depend on the AKAP-Lbc/Rho signaling cascade. To understand the downstream way, we performed RNA-seq analyses between normal and AKAP-Lbc-depleted hESCs using the doxycyclin-inducible gene silensing strategy. Overall design: We use the genetically modified hESCs in which AKAP-13-targeting shRNA is induced by doxycyclin(dox) treatment. To minimize cell loss during treatment, anti-apoptotic factor Bcl-XL is overexpressed. We collected RNA from dox-treated and untreated cells in biological triplicate. We measured gene expression in these 2 sample groups using RNA-seq (illumina HiSeq) .
Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells.
No sample metadata fields
View SamplesThe transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Using laser capture microscopy and microarray analysis, a population of genes rapidly induced by light in the suprachiasmatic nucleus is identified.
Identification of novel light-induced genes in the suprachiasmatic nucleus.
No sample metadata fields
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