To identify molecules to serve as diagnostic markers for high-grade prostate cancer (PC) and targets for novel therapeutic drugs, we investigated the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection.
The ubiquitin-like molecule interferon-stimulated gene 15 is overexpressed in human prostate cancer.
Specimen part
View SamplesPreviously, we constructed a coculture model to analyze the effect of macrophages on intestinal epithelial cells, and found that TNF-a secreted from human macrophage-like THP-1 cells induced cell damage to intestinal epithelial Caco-2 cells (Exp.Cell.Res. 2006, 312(19):3909-19). In this study, we present activation of NF-kB in Caco-2 cells within 15 min after coculturing. To reveal how TNF-a secreted from THP-1 cells affects Caco-2 cells in an early stage of coculture, we exhaustively analyzed the changes of gene expression in Caco-2 cells cocultured with THP-1 cells over the time periods of 0, 1, 3, 6, 24, and 48 h by using a DNA microarray. Differentially expressed genes extracted with maSigPro demonstrated that IEX-1 was the lowest p-value gene, that is, the most significantly changed gene among the up-regulated genes. The genes expressed in a similar pattern to IEX-1 involved immunity, apoptosis, and protein kinase cascade. These findings suggest that the stimuli of TNF-a from THP-1 cells activates NF-kB, leading induction of various gene expression. This pattern of gene expression indicates that not only early defense response but also cell death occurs at the same time, causing inflammatory condition.
Transient up-regulation of immunity- and apoptosis-related genes in Caco-2 cells cocultured with THP-1 cells evaluated by DNA microarray analysis.
Cell line, Time
View SamplesThe identification of genes that contribute to the biological basis for clinical heterogeneity and progression of prostate cancer is critical to accurate classification and appropriate therapy. We performed a comprehensive gene expression analysis of prostate cancer using oligonucleotide arrays with 63,175 probe sets to identify genes and expressed sequences with strong and uniform differential expression between nonrecurrent primary prostate cancers and metastatic prostate cancers. The mean expression value for >3,000 tumor-intrinsic genes differed by at least 3-fold between the two groups. This includes many novel ESTs not previously implicated in prostate cancer progression. Many differentially expressed genes participate in biological processes that may contribute to the clinical phenotype. One example was a strong correlation between high proliferation rates in metastatic cancers and overexpression of genes that participate in cell cycle regulation, DNA replication, and DNA repair. Other functional categories of differentially expressed genes included transcriptional regulation, signaling, signal transduction, cell structure, and motility. These differentially expressed genes reflect critical cellular activities that contribute to clinical heterogeneity and provide diagnostic and therapeutic targets.
Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWe created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.
Pathophysiological and molecular mechanisms involved in renal congestion in a novel rat model.
Sex, Specimen part
View SamplesMouse FGF15 and human FGF19 are orthologous proteins that regulate bile acid metabolism. However, other hepatic functions of FGF15/19 are not well characterized.
FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway.
Sex, Specimen part
View SamplesCancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Specimen part, Cell line
View SamplesThe heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here we sought to define the extra-cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac over-expression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression and metabolite levels in heart and liver but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild-type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra-cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues. Overall design: n=3 for each genotype and organ
MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver.
No sample metadata fields
View SamplesThe purpose of this experiment was to compare the gene expression pattern between wild-type and Trib1-deficient macrophages in response to LPS.
Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View Samples