63 melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 oligo arrays. The aim of this study was to identify potential downstream targets of key oncogenes and TSGs in melanoma (including p14ARF, p16INK4A, BRAF etc).
Confirmation of a BRAF mutation-associated gene expression signature in melanoma.
No sample metadata fields
View SamplesTumor suppressor genes (TSGs) are sometimes inactivated by transcriptional silencing through promoter hypermethylation. To identify novel methylated TSGs in melanoma, we carried out global mRNA expression proling on a panel of 12 melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC) and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene expression after drug treatment was assessed using Illumina whole-genome microarrays. After qRT-PCR conrmation, we followed up 8 genes (AKAP12, ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by quantitative DNA methylation analysis using mass spectrometry of base-specic cleaved amplication products in panels of melanoma cell lines and fresh tumors. PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 3559% of the melanoma cell lines compared to melanocytes and which was correlated with a high proportion of promoter methylation (>4060%). The same genes also showed extensive promoter methylation in 625% of the tumor samples, thus conrming them as novel candidate TSGs in melanoma.
Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma.
Disease, Disease stage, Cell line, Treatment
View Samples35 Melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 microarrays were analysed for genes differentially expressed between cell lines carrying wild-type p14ARF and those with mutant 14ARF. All of these cell lines contained wild-type p53 (so that the effects of p14ARF mutations could be analysed without contamination from p53).
Gene expression profiling in melanoma identifies novel downstream effectors of p14ARF.
No sample metadata fields
View Samplesused to identify differences between tissues from patients undergoing surgery for BPH with unresolved symptoms compared to incidental BPH from patients with prostate cancer
Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.
Specimen part
View SamplesTo identify genes dysregulated in bipolar disorder (BD1) we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by 1.3-fold in 3 BD1 cases compared to their co-twins, and which were statistically (p 0.05) differentially expressed between the groups of BD1 cases and controls. Using qRT-PCR we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1, and PI4KCB, in at least 2 of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design1 our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis we identified up-regulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.
Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway.
Sex
View SamplesThe process of lung squamous carcinoma tumorigenesis and metastasis is poorly characterized. Additionally, few models of this process exist in an immune-competent context. In order to address this problem, we utilized the KLN-205 lung squamous carcinoma cell lines that is derived from carcinogen exposure in DBA2 mice.
Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking.
Specimen part
View SamplesThe expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression.
Sex, Age, Cell line
View SamplesObjective:
Gene expression analysis in absence epilepsy using a monozygotic twin design.
Sex
View SamplesThe nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist.
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
No sample metadata fields
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