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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
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to assess gene expression profiling of 6 patients with a mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene (INSR) and 10 matched healthy controls
Publication Title
A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Existing controversy regarding the importance of AMP-activated protein kinase (AMPK) in fatty acid (FA) oxidation in skeletal muscle with contraction/exercise may to some extent pertain to redundant AMPK1 signaling. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO) we hypothesized that FA utilization would be impaired in skeletal muscle. Calorimetric analysis showed a similar respiratory exchange ratio (RER) of AMPK WT and mdKO mice when fed normal chow, a high fat diet or with prolonged fasting. Though, in vivo treadmill exercise at the same relative intensity induced a higher RER in mdKO mice compared to WT (WT=0.81; mdKO=0.87; p<0.01) indicating a decreased utilization of FA. Ex vivo incubation of soleus muscle revealed that basal and contraction-induced FA oxidation was impaired in mdKO mice, suggesting that the increased RER during in vivo running exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 and FABPpm (by 17-40%) together with abolishment of TBC1D1 Ser237 phosphorylation in mdKO mice, may result in lower FA transport capacity and FA transport protein translocation to sarcolemma, respectively. In summary this study shows that the catalytically active AMPK subunits are required for normal stimulation of FA utilization during exercise and contractions.
Publication Title
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression was compared between E18.5 E-cadherin conditional knockout (cKO) small intestine and E18.5 control mouse small intestine.
Publication Title
E-cadherin is required for intestinal morphogenesis in the mouse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The aim of this study was to explore what molecular and cellular processes predicate the conversion from insulitis to diabetes. The transcriptional profiles of CD45+ immune cells collected from pancreas of a cohort of age-matched female mice, which were scanned by MRI to determine the risk of diabetes development.
Publication Title
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 396 Downloadable Samples
Illumina HiSeq 2000
Description
In order to understand the effect of genetic background on the response to gene dose perturbation, we performed mRNA transcriptional profiling on 99 hemizygotic lines (Df/+) from the DrosDel project, which have hybrid genetic background of OregonR/w1118. Overall design: We performed RNA-Seq analysis of 417 single adult flies in duplicate or triplicate. Flies are from 73 different genotypes. Differential gene expression was analyzed separately for each sex, gene expression from each genotype was compared to normalized mean of gene expression remaining 72 genotypes.
Publication Title
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sample Metadata Fields
Sex, Subject
View Samples- Drosophila melanogaster
- 343 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed mRNA transcriptional profiling on 99 hemizygotic lines (Df/+) from the DrosDel project covering 68% of chromosome 2L, in order to understand how changes in gene copy number affect overall transcriptome. Overall design: We performed RNA-Seq analysis on 396 pools of 15-25 adult flies each. Samples include males or females from 99 different genotypes in duplicate. Differential gene expression was analyzed separately for each sex, by comparing each genotype with the remaining 98.
Publication Title
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Drosophila melanogaster
- 247 Downloadable Samples
- Illumina HiSeq 2000
Description
To measure the response to gene dose, we performed mRNA-Seq of fly heads with molecularly defined deletions constructed from DrosDel deficiency lines (Ryder et al. Genetics 2007, 177(1):615-29) on the Illumina HiSeq 2000 platform. Overall design: We performed single-end next-generation sequencing (RNA-Seq) on poly-A+ RNA extracted from adult female and male heads in biological triplicate. Besides wildtype females (XX) and males (XY) that were heterozygous for deletions, we also sequenced females that were transformed into males (XX males) by using mutations in the sex determination gene transformer-2 (tra2). The original lines with deletions, including 22 deletions on the chromosome X and 12 deletions on the chromosome 3L, were from the DrosDel project. The diploid controls without DrosDel deletions were derived from w1118 (the parental line of DrosDel stocks) or Oregon-R Strain. We sequenced a total of 249 samples.
Publication Title
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sample Metadata Fields
Sex, Subject
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
We used RNA-seq to monitor mRNA levels of all genes in response to hypoxia of wild-type yeast, S. cerevisiae (strain yMH914 with wildtype HAP1). To gain insights into how gene expression changes over time, cells were subjected to 100% nitrogen gas and collected after 0,5,10,30,60,120,180, and 240 minutes. Total RNA was extracted and mRNAs were enriched by polyA selection. The cDNA was prepared into a sequencing library, multiplexed and single-end sequenced by an Illumina HiSeq 2500 sequencer. After mapping with Tophat2, the number of reads per feature was calculated using HTSeq. Overall design: RNA-seq analysis of eight time points of a yeast strain grown in hypoxia. There are three biological replicates of the time course.
Publication Title
Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting, but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy.
Publication Title
Extracellular matrix protein CCN1 limits oncolytic efficacy in glioma.
Sample Metadata Fields
Cell line
View Samples