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GSE5913
Mus musculus
37 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We have used microarray technology to identify the transcriptional targets of Rho subfamily GTPases. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of biological functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are up-regulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc, and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells
Publication Title
Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells.
Publication Title
Long-term reduction of T-cell intracellular antigens reveals a transcriptome associated with extracellular matrix and cell adhesion components.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina Genome Analyzer IIx
Description
This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1- and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenotypes. The data of differential expression were validated by using genome-wide microarrays and QPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Taken together, these results indicate that differential gene expression, alternative pre-mRNA isoforms, promoter usage and microRNA profiling contribute to define the molecular expression phenotypes implied in the progression of proliferative phenotypes associated to the absence of TIA proteins and prioritize candidates for future study. Overall design: Each library was run on one RNASeq Multiplex of 76 bp using sequencing from Illumina Genome Analyzer (GAIIx). Three samples were analyzed in this manner, taken from control, TIA1 and TIAR shRNA-depleted HeLa cells.
Publication Title
Long-term reduction of T-cell intracellular antigens reveals a transcriptome associated with extracellular matrix and cell adhesion components.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization.
Publication Title
The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We used manual macrodissection or laser capture microdissection (LCM) to isolate tissue sections of the hippocampus area of Ras-GRF1 wild type and knockout mice brains, and analyzed their transcriptional patterns using commercial oligonucleotide microarrays. Comparison between the transcriptomes of macrodissected and microdissected samples showed that the LCM samples allowed detection of significantly higher numbers of differentially expressed genes, with higher statistical rates of significance. These results validate LCM as a reliable technique for in vivo genomic studies in the brain hippocampus, where contamination by surrounding areas (not expressing Ras-GRF1) increases background noise and impairs identification of differentially expressed genes. Comparison between wild type and knockout LCM hippocampus samples revealed that Ras-GRF1 elimination caused significant gene expression changes, mostly affecting signal transduction and related neural processes. The list of 36 most differentially expressed genes included loci concerned mainly with Ras/G protein signaling and cytoskeletal organization (i.e. 14-3-3/, Kcnj6, Clasp2) or related, cross-talking pathways (i.e. jag2, decorin, strap). Consistent with the phenotypes shown by Ras-GRF1 knockout mice, many of these differentially expressed genes play functional roles in processes such as sensory development and function (i.e. Sptlc1, antiquitin, jag2) and/or neurological development/neurodegeneration processes affecting memory and learning. Indeed, potential links to neurodegenerative diseases such as Alzheimer disease (AD) or Creutzfeldt-Jacobs disease (CJD), have been reported for a number of differentially expressed genes identified in this study (Ptma, Aebp2,Clasp2, Hebp1, 14-3-3/, Csnk1, etc.). These data, together with the previously described role of IRS and insulin (known Ras-GRF1 activators) in AD, warrant further investigation of a potential functional link of Ras-GRF1 to neurodegenerative processes.
Publication Title
Laser microdissection and microarray analysis of the hippocampus of Ras-GRF1 knockout mice reveals gene expression changes affecting signal transduction pathways related to memory and learning.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligands activation of RXR modulate host antivarl response. We used microarray to determine if 9cRA could regulate the antiviral gene expression in LPS- and polyI:C triggered RAW264.7 cells.
Publication Title
Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloidderived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohns Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria.
Publication Title
The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 15 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
We studied the influence of the oleic acid content of the diet on adipose tissue transcriptome.
Publication Title
Dietary energy source largely affects tissue fatty acid composition but has minor influence on gene transcription in Iberian pigs.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Sus scrofa
- 26 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
We studied the influence of genetic type (pure Iberian pigs vs crossbred with Duroc) on l.dorsi transcriptome
Publication Title
Longissimus dorsi transcriptome analysis of purebred and crossbred Iberian pigs differing in muscle characteristics.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is a mind aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Gene set enrichment analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.
Publication Title
Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples