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GSE40564
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study we investigated the potential of targeting the catalytic class IA PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types. Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or down-regulation by small interfering RNA. Results: Over-expression of the PI3K isoforms p110 and p110 was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110 with RNA interference (RNAi) or selective pharmacological inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo, while targeting p110 was less effective. Inhibition of p110 also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mammalian target of rapamycin (mTOR) pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). A DNA microarray analysis revealed that p110 inhibition profoundly affected the balance of pro- and anti-apoptotic Bcl-2 family proteins. Finally, p110 inhibition led to impaired SCLC tumor formation and vascularization in vivo. Conclusion: Together our data demonstrate the key involvement of the PI3K isoform p110 in multiple tumor-promoting processes in SCLC.
Publication Title
Targeting the phosphoinositide 3-kinase p110-α isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the CAR-, PXR- and PPAR-specific genome-wide expression changes, hepatocyte cultures from six individual donors were treated with the prototypical ligands for
Publication Title
Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Statins are widely used cholesterol-lowering drugs that inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis. In some cases, however, these drugs may cause a number of toxic side effects in hepatocytes and skeletal muscle tissue. Currently, the specific molecular mechanisms that cause these adverse effects are not sufficiently understood. In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at five time points upon atorvastatin treatment. A novel systems-level analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor binding specificities, protein-protein interactions and protein-drug interactions. Several previously unknown transcription factors, regulatory cofactors and signaling molecules were found to be involved in atorvastatin-responsive gene expression. Some novel relationships, e.g., the regulatory influence of nuclear receptor NR2C2 on CYP3A4, were successfully validated in wet-lab experiments.
Publication Title
Inferring statin-induced gene regulatory relationships in primary human hepatocytes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 139 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements.
Publication Title
MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used microarrays to study the changes in the transcriptional profile upon Snail knockdown in murine lung adenocarcinomas
Publication Title
Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating immune cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used microarrays to study the changes in the transcriptional profile upon Snail overexpression in murine lung adenocarcinomas
Publication Title
Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating immune cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103CD11b+ DC subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.
Publication Title
TGFβR signalling controls CD103<sup>+</sup>CD11b<sup>+</sup> dendritic cell development in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Publication Title
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Publication Title
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histone acetyltransferases (HATs) and deacetylases (HDACs) function antagonistically to control histone acetylation. As acetylation is a histone mark for active transcription, HATs have been associated with active and HDACs with inactive genes. We describe here genome-wide mapping of HATs and HDACs binding on chromatin and nd that both are found at active genes with acetylated histones. Our data provide evidence that HATs and HDACs are both targeted to transcribed regions of active genes by phosphorylated RNA Pol II. Furthermore, the majority of HDACs in the human genome function to reset chromatin by removing acetylation at active genes. Inactive genes that are primed by MLL-mediated histone H3K4 methylation are subject to a dynamic cycle of acetylation and deacetylation by transient HAT/HDAC binding, preventing Pol II from binding to these genes but poising them for future activation. Silent genes without any H3K4 methylation signal show no evidence of being bound by HDACs.
Publication Title
Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes.
Sample Metadata Fields
Specimen part, Treatment
View Samples