Genome-wide gene expression profile of human gastric cancer
Ontology highlight
ABSTRACT: We performed microarray experiments on gastric tissue samples to identify the differential expression patterns between tumor and normal condition. 40 gastric tumor tissue samples, 12 normal gastric tissue samples
Project description:Transcriptional profiling of estrogen regulated genes in human primary osteoblasts. The cells were either treated with estradiol (1 nM) or the pure antagonist ICI 182,780 (Faslodex), which acts as a potent inhibitor of estrogen receptor signaling.
Project description:CCN5 is a member of the CCN (Connective Tissue Growth Factor/Cysteine-rich 61/Nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that CCN5 protein is localized mostly in the cytoplasm, and in part in the nucleus, of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor, presumably through association with histone deacetylase HDAC1. Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the TGF-beta signaling pathway, prominent among them TGF-betaRII receptor. We show that CCN5 is recruited to the TGF-betaRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-betaRII gene. Consistent with this finding, we found that CCN5 functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT. We performed microarray gene expression profiling of one MCF-7-sh-CCN5 sample and one MCF-7-sh-scrambled sample (control sample).
Project description:Stimulation of the mouse hindlimb via the sciatic nerve was used to induce contractions for 4 hours to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 + 0.1 g/g body weight) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon completion of the study. An immediate-early growth response was present in the EDL (FOS, JUN, ATF3, MAFK) with a similar but attenuated pattern in the soleus. Transcript profiles showed decreased fast fiber specific mRNA (myosin heavy chains 2A, 2B; troponins T3, I; -tropomyosin, m-creatine kinase) and increased slow transcripts (myosin heavy chain slow/1, troponin C, tropomyosin 3) in the EDL. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration or myofiber damage in stimulated vs. control muscles. Several fiber type specific transcription factors (EYA1, TEAD1, NFATc1 and c4, PPARG, PPARGC1 and β, BHLHB2) increased in the EDL along with transcription factors characteristic of embryogenesis (KLF4, SOX17, TCF15, PKNOX1, ELAV). No established in vivo satellite cell markers or the genes activated during our parallel studies of satellite cell proliferation in vitro (CYCLINS A2, B2, C, E1, MyoD) increased in the stimulated muscles. These data indicated that onset of fast to slow phenotype conversion occurred in the EDL within 4 hours of stimulation without satellite cell recruitment or muscle injury but was driven by phenotype specific transcription factors from resident fiber myonuclei including activation of nascent developmental transcriptional programs. Adult male Swiss Webster mice (30-35 g) were anesthetized, a bipolar electrode was implanted adjacent to the sciatic nerve and the hindlimb immobilized. The voltage-force relation was determined to establish supramaximal stimulation conditions and the length-tension relation was determined to set the resting length for maximum twitch tension. Contractions were induced by sciatic nerve stimulation (0.5 msec duration, 2-5 volts). The muscles were allowed to rest 15 minutes for full metabolic recovery at physiologic temperatures. Supramaximal stimulation was applied at a rate of 10 Hz for 4 hours. At the end of each experiment the soleus muscles were carefully dissected and flash frozen in liquid nitrogen for analysis of mRNA expression via microarray analysis. The contralateral, unstimulated Soleus provided a genetically matched, paired control for each specimen.
Project description:There is no accurate and well-validated short-term test for non-genotoxic carcinogens, necessitating an expensive two year rodent bioassay before a risk assessment can begin. We have developed a short-term in vivo rat assay that predicts whether non-genotoxic chemicals are likely to induce hepatic tumors based on transcript profiles in the liver. Using a large independent test set, assay accuracy was found to be superior to existing pathological and genomic markers. Comparison of the test chemical's signature profile to reference carcinogens of known mechanism can also identify a potential mode(s) of action, allowing an early assessment of human cancer risk. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: dose response, time course, compound treatment Treatment of male Sprague-Dawley rats with 147 non-genotoxic compounds at various doses and durations, in biological triplicate, along with vehicle-matched control animals. Liver samples were assayed for gene expression. Hepatocarcinogenic and non-carcinogenic compounds were included. A classifier for carcinogenicity was built on a training set of 25 carcinogens and 75 noncarcinogens (randomly selected compounds, maximum tolerated dose, 5 day timepoints), and tested on the remaining 47 compounds at various timepoints. A total of 990 samples were hybridized to single-channel CodeLink RU1 arrays. Biological triplicates were combined with matched control samples to calculate log ratios.
Project description:A definition of RNA expression changes that correlate with liver response programs and an understanding of the similarities and differences in responses to different classes of chemicals would aid in new chemical or drug characterization and add to our understanding of liver biology. We have used a supervised classification approach to systematically mine a large microarray database derived from livers of compound-treated rats. Thirty-four distinct signatures (classifiers) for pharmacological and toxicological endpoints resolvable by gene expression can be identified. The contribution of genes to signatures is not correlated to average expression or amplitude of regulation, and pre-selection of genes can significantly reduce signature performance. Just 200 genes are sufficient to classify all endpoints and can form the basis of a small diagnostic array useful in toxicogenomics. Signature genes were enriched in xenobiotic and acute phase response genes as well as un-annotated genes, suggesting that not all key genes in liver xenobiotic responses have been identified. Individual signatures can be re-derived up to 25 times from a gene set cyclically .stripped. of the signature genes. The union of these non-overlapping sets was used to describe the biological mechanisms of liver fibrosis. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: dose response, time course, compound treatment Treatment of male Sprague-Dawley rats with 344 compounds at various doses and durations, in biological triplicate, along with vehicle-matched control animals. Liver samples were assayed for gene expression. A total of 1695 samples were hybridized to single-channel CodeLink RU1 arrays. Biological triplicates were combined with matched control samples to calculate log ratios. Classifiers were generated and evaluated for 2112 biological questions, resulting in 34 distinct, high-performance "signatures."
Project description:This SuperSeries is composed of the following subset Series: GSE22615: Genomic alterations of chromosome 11 induce transcriptomic dysregulation in aggressive and malignant prolactin tumours GSE22812: Transcriptomic dysregulation in aggressive and malignant prolactin tumours Refer to individual Series
Project description:In the process of evaluating teratogenic properties of xenobiotica, the consumption of laboratory animals is high and costly which makes the development of alternative methods desirable. The pluripotent embryocarcinoma cell line P19, which closely resembles the early stage of an embryo, may be relevant as an in vitro model of teratogenicity. The antiepileptic drug Valproic acid (VPA) is a potent inducer of neural tube defects (ntd:s) in both human and mouse, but its mechanism of teratogenicity is not know. P19 cells were here treated with sodium valproate in a both time and dose dependent matter to profile the gene expression response with Codelink UniSet Mouse 20K I Bioarrays. This profile may reveal biomarkers of ntd:s as well as give mechanistic input of the teratogenicity of VPA.
Project description:Stomatal guard-cells modulate gas exchange between the plant and the atmosphere.<br><br>Regulation of transcription is emerging as an important mechanism in<br><br>controlling guard cells activity. The Arabidopsis transcription factor<br><br>AtMYB60, is specifically expressed in guard cells and controls stomatal<br><br>movements. Opening of stomatal pores is constitutively reduced in the<br><br>atmyb60-1 null allele, and water loss during drought is diminished in<br><br>the mutant compared to wild type. To address the effect of the AtMYB60<br><br>disruption on global gene expression, total mRNAs, derived from<br><br>atmyb60-1 and WT rosette leaves, grown in standard conditions, were hybridized to a cDNA microarray.