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GSE12692
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Ewing Tumors (ET) are highly malignant tumors, localized in bone or soft tissue and are molecularly defined by ews/ets translocations. We identified histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. EZH2s suppressive activity maintains stemness in normal and malignant cells. Here we found EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in ET and mesenchymal stem cells. Downregulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis in immunodeficient Rag2-/-C-/- mice was suppressed. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. Downregulation of EZH2 decreased histone H3 lysine 27 trimethylation (H3K27me3) at target loci. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR) as well as genes involved in neuroectodermal differentiation (EMP1, EPHB2, GFAP, GAP43). These data suggest that EZH2 might play a central role in Ewing Tumor pathology shaping the oncogenicity and stem cell phenotype of this tumor presumably by epigenetic regulation.
Publication Title
EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The antioxidant response element (ARE) is a cis-acting regulatory enhancer element found in the 5 flanking region of many phase II detoxification enzymes. Upregulation of ARE-dependent target genes is known to have neuroprotective effects; yet, the mechanism of activation is largely unknown. By screening an arrayed collection of approximately 15,000 full-length expression cDNAs in the human neuroblastoma cell line IMR-32 with an ARE-luciferase reporter, we have identified several cDNAs not previously associated with ARE activation. A subset of cDNAs, including sequestosome 1 (SQSTM1) and dipeptidylpeptidase III (DPP3), activated the ARE in primary mouse-derived cortical neurons. Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NRF2 nuclear translocation and led to increased levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), a protein which is transcriptionally regulated by the ARE. When transfected into IMR-32 neuroblastoma cells that were depleted of transcription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induce NQO1 expression, indicating that the ARE activation upon ectopic expression of these cDNAs is mediated by NRF2. Studies with pharmacological inhibitors indicated that 1-phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) signaling are also essential for activity. Lastly, overexpression of these cDNAs conferred partial resistance to hydrogen peroxide induced toxicity, consistent with the induction of antioxidant and phase II detoxification enzymes which can protect from oxidative stress. This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress, and a novel therapeutic approach to degenerative diseases and aging.
Publication Title
A genomic screen for activators of the antioxidant response element.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 4 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Quorum sensing (QS) is a mechanism of bacterial gene regulation in response to increases in population density. Production of small molecule QS signals, their accumulation within a diffusion-limited environment and their binding to the LuxR-type receptor trigger QS-controlled gene regulatory cascades. QS pathways mediated by acylhomoserine lactones (AHLs) in Gram-negative bacteria are the best studied. In Pseudomonas aeruginosa, for example, binding of AHLs to their cognate receptors (LasR, RhlR) controls production of virulence factors, pigments, antibiotics and other behaviors important for its interactions with eukaryotic hosts and other bacteria. We isolated a new small cyclopropane-containing fatty acid, lyngbyoic acid (1), as a major metabolite of the marine cyanobacterium, Lyngbya sp., collected off Fort Pierce, Florida. The structure of 1 was determined by NMR, MS and optical rotation. We screened 1 against four reporters based on AHL receptors from Vibrio fischeri (LuxR), Aeromonas hydrophila (AhyR), Agrobacterium tumefaciens (TraR) and P. aeruginosa (LasR) and found that 1 most strongly affected LasR. We show, by using a defined set of reporters, that compound 1 acts both through the AHL-binding site of LasR and independent of it. We also show that 1 reduces pyocyanin and LasB, both on the protein and transcript level, in wild-type P. aeruginosa, and that 1 directly inhibits LasB enzymatic activity. Conversely, dodecanoic acid (11) increased pyocanin and LasB, demonstrating that 1 is a tagged fatty acid potentially resistant to -oxidation.
Publication Title
Lyngbyoic acid, a "tagged" fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05, fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis.
Publication Title
Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histone deacetylases (HDACs) regulate gene expression. Inhibition of class I HDACs has been shown to inhibit cancer cell growth. Largazole, a new potent HDAC inhibitor, shows strong antitumor activity, presumably by modulating transcription of cancer relevant genes.
Publication Title
Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Total RNA was extracted from apratoxin A or vehicle treated HT29 cells using the RNeasy Mini Kit (Qiagen). Probe values from CEL files were condensed to probe sets using Rosetta Resolver software. Resolver ANOVA analysis was then performed between groups.
Publication Title
A functional genomics approach to the mode of action of apratoxin A.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
Publication Title
CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
To elucidate the mode of action of apratyramide, we performed microarray profiling using the Affymetrix GeneChip Human Transcriptome Array 2.0 to determine global changes in transcript levels in HaCaT cells treated with apratyramide. Comparativel analysis identified 371 differentially expressed genes after 12 h treatment with 30 M apratyramide (p < 0.05, FDR corrected, fold change >1.5 or <0.67). Consistent with our previous data, VEGF-A appeared to be one of the most up-regulated genes. To examine the molecular functions and genetic networks, the microarray data was analyzed using Ingenuity Pathways Aanalysis (IPA).The global changes of transcript levels are associated with increased downstream phenotypic effects including angiogenesis, mitogenesis, differentiation of epithelial tissue and formation of skin, and decreased effects such as apoptosis of liver cells and hypoplasia of organs. IPA analysis of 371 microarray hits indicated the unfolded protein response (UPR) as the top canonical pathway with a p-value of 1.45 10-16. The IPA also elucidated that the 371 hits were most related to a molecular network associated with the function of cellular compromise and cellular maintenance. The network contains molecular components from UPR pathway, NRF2-mediated oxidative stress response signaling as well as glucocorticoid receptor signaling.
Publication Title
Apratyramide, a Marine-Derived Peptidic Stimulator of VEGF-A and Other Growth Factors with Potential Application in Wound Healing.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Publication Title
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Sample Metadata Fields
Specimen part
View Samples