Characterization of Peroxisome Proliferator-Activated Receptor alpha (PPAR(alpha)) - Independent Effects of PPAR(alpha) Activators in the Rodent Liver: Di-(2-ethylhexyl) phthalate Activates the Constitutive Activated Receptor
Characterization of peroxisome proliferator-activated receptor alpha--independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor.
Sex, Age, Treatment
View SamplesAnalysis of livers of male and female B6C3F1 mice exposed to prototype treatments from five classes of model hepatotoxicants. These hepatotoxicants include compounds that activate the peroxisome proliferator-activated receptor (PPAR), induce the inflammatory response, activate the constitutive androstane receptor (CAR), stimulate the hypoxia signal transduction pathway, and activate the aryl-hydrocarbon receptor (AHR). The results provide insights into the shared and unique pathways that are activated across these model hepatotoxicants.
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sex, Age, Compound, Time
View SamplesPPAR-null and wild-type male mice treated with PFHxS or PFNA
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sex, Specimen part, Compound
View SamplesMany environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist.
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sex, Specimen part, Compound
View SamplesNascent transcription profiles are shown for scaled megadomains and 100kb flanking regions before BRD4-NUT induction (0h) and at different time points (2h, 3h, 7h) following induction in 293T cells. Increase of the transcription from 0h to 7h after induction. Average level of transcriptional activity is reduced within the megadomains and their flanking regions following JQ1 treatment of TC-797 cells. Profile of nascent RNA-seq is shown for cells without JQ1 treatment, and for cells 1hr, 2.5hr and 4hr following JQ1 treatment. Overall design: Recovery and analysis of nascent RNA
The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains.
No sample metadata fields
View SamplesTranscriptome analysis on ING5-knockdown brain tumor stem cell lines
ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways.
Specimen part, Cell line
View SamplesCK1-alpha-LS was knocked down in human coronary artery smooth muscle cells. Gene level and exon level changes in expression were assessed.
Protein kinase CK1alphaLS promotes vascular cell proliferation and intimal hyperplasia.
Specimen part
View SamplesBasal-like breast cancer (BLBC) cells share phenotypic similarities with cancer stem cells (CSCs) but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin v3, are highly expressed in a subset of BLBC cell lines as well as in cancer stem cell-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin 3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-B-mediated transcription of key cytokines, namely IL6 and IL8, which in turn mediate downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.
Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.
Sex, Specimen part
View SamplesWe examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-B as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAs efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy.
Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.
Sex, Specimen part
View Samples