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Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The crizotinibresistant ALKF1174L mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel ALK inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALKF1174L. Here we demonstrate acquired resistance to TAE684 and LDK378 in ALKF1174L-driven human NB cells that is linked to overexpression and activation of the AXL tyrosine kinase and epithelial-to-mesenchymal transition (EMT). AXL phosphorylation conferred TAE684 resistance to NB cells through upregulated ERK signaling. Inhibition of AXL partly rescued TAE684 resistance, resensitizing these cells to this compound. AXL activation in resistant cells was mediated through increased expression of the active form of its ligand, GAS6, which also served to stabilize the AXL protein. Although ectopic expression of AXL and TWIST2 individually in TAE684-sensitive parental cells led to the elevated expression of mesenchymal markers and invasive capacity, only AXL overexpression induced resistance to TAE684 as well. TAE684-resistant cells showed greater sensitivity to HSP90 inhibition than did their parental counterparts, with downregulation of AXL and AXL-mediated ERK signaling. Our studies indicate that aberrant AXL signaling and development of an EMT phenotype underlie resistance of ALKF1174L-driven NB cells to TAE684 and its derivatives. We suggest that the combination of ALK and AXL or HSP90 inhibitors be considered to delay the emergence of such resistance.
Publication Title
ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chronically dysregulated NOTCH1 interactome in the dentate gyrus after traumatic brain injury.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
SPT6, encoded by the SUPT6H in humans and Supt6 in mice, respectively, is a conserved histone chaperone that interacts with RNA polymerase II and participates in transcription elongation. However, the question of how SPT6 comes into play in transcriptional activation upon signaling, particularly in mammalian cells, has remained elusive. We investigated the contribution of SPT6 to interferon beta (IFNbeta) induced transcription in mouse NIH3T3 cells. IFNbeta triggers rapid and high level transcription of many IFN-stimulated genes (ISGs). We report here that SPT6 is recruited to ISGs after IFN stimulation. This recruitment was dependent on the interaction with the methyltransferase, NSD2. Further, siRNA-based SPT6 knockdown reduced levels of ISG activation. RNA-Seq analysis showed that SPT6 knockdown diminished about 50% of ISGs whose induction levels were higher than those unaffected by SPT6 knockdown. Under the tested conditions, SPT6 knockdown did not measurably change expression of constitutively expressed genes. This report highlights that SPT6 is recruited in a stimulus-dependent manner and elicits a major impact on signal induced transcription. Overall design: RNA-seq of NIH3T3 cells.
Publication Title
SPT6 interacts with NSD2 and facilitates interferon-induced transcription.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Peroxisome proliferator-activated receptor beta/delta protects against obesity by reducing dyslipidemia and insulin resistance via effects in various organs, including muscle, adipose tissue, liver, and heart. However, nothing is known about the function of PPAR-beta in pancreas, a prime organ in the control of glucose metabolism. To gain insight into so far hypothetical functions of this PPAR isotype in insulin production, we specifically ablated Ppar-beta in pancreas. The mutated mice developed a chronic hyperinsulinemia, due to an increase in both beta-cell mass and insulin secretion. Gene expression profiling indicated a broad repressive function of PPAR-beta impacting the vesicular compartment, actin cytoskeleton, and metabolism of glucose and fatty acids. Analyses of insulin release from the islets revealed an increased second-phase glucose-stimulated insulin secretion. Higher levels of PKD, PKC-delta and diacyglycerol in mutated animals lead to an enhanced formation of trans-Golgi network (TGN)-to-plasma-membrane transport carriers in concert with F-actin disassembly, which resulted in increased insulin secretion and its associated systemic effects. Taken together, these results provide evidence for PPAR-beta playing a repressive role on beta-cell growth and insulin exocytosis, which shed new light on its anti-obesity action.
Publication Title
PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To find out genes regulated by geranylgeraniol (GGOH) treatment in peritoneal macrophage, we compared gene expression of cells treated with 200ng ml LPS and 250 micromolar compactin versus 200ng ml LPS, 250 micromolar compactin and 100micromolar GGOH.
Publication Title
Sufficient production of geranylgeraniol is required to maintain endotoxin tolerance in macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcript profile of apices of 20 days-old Arabidopsis plants over expressing miR396b.
Publication Title
Repression of cell proliferation by miR319-regulated TCP4.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
[original title] Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
Publication Title
Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
Sample Metadata Fields
Disease, Disease stage
View Samples
GSE11250- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcript profile of 10 days-old seedlings over expressing miR396
Publication Title
Control of cell proliferation in Arabidopsis thaliana by microRNA miR396.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 101 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Analysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples