Gene expression of human paediatric osteosarcoma tumour samples relative to normal human osteoblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Bekim Sadikovic
PROVIDER: E-GEOD-12865 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Sadikovic Bekim B Yoshimoto Maisa M Chilton-MacNeill Susan S Thorner Paul P Squire Jeremy A JA Zielenska Maria M
Human molecular genetics 20090313 11
Altered gene expression in tumors can be caused by copy number alterations to DNA or mutation affecting coding or regulatory regions of genes. However, epigenetic events may also influence gene expression. Malignant cells can show major disruptions in DNA methylation profiles, which are manifested as aberrant hypermethylation or as hypomethylation of gene promoters, as well as global genomic hypomethylation. In this study we performed integrative whole-genome analysis of DNA copy number, promote ...[more]
Similar Datasets
Project description:Gain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions. Cancer-specific changes in gene expression play an essential role in cancer occurrence, and ultimately lead to cancer-related self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, angiogenesis, and metastasis. We aimed to analyse such changes in gene expression related to osteosarcoma. Keywords: Comparative We performed genome-wide comparison of gene expression and identified genes that are differentialy expressed in osteosarcoma (U2OS, MG63) cell lines relative to normal human osteoblasts (HOB)
2009-05-01 | E-GEOD-11414 | biostudies-arrayexpress
Project description:This study was performed with an overall aim to compare gene expression prolife in human sarcoma cell lines and in primary untransformed cells. Individual Cell Lines were collected from ATCC, DSMZ, HPA Cultures, Clonetics, Wolfson Insitute for Biomedical Research Cell bank, UCL, London, U.K. or were a gift from other researchers.
2013-01-01 | E-GEOD-39262 | biostudies-arrayexpress
Project description:Comparison of ATG gene family members in MPN pattients with normal controls One-Way ANOVA while contrasting ATG gene family members in 11 Normal (Control) with either 1) 13 PV samples 2) 24 ET samples or 3) 18 PMF samples
2015-03-31 | E-GEOD-38543 | biostudies-arrayexpress
Project description:Background: Ameloblast differentiation is the most critical stepwise process in amelogenesis and controlled by a precisely molecules synergistically. To better understand the molecular events defining cell differentiation between preameloblasts and secretory ameloblasts during amelogenesis, a more precise identification of molecules and signaling networks would shed light on the mechanisms governing enamel formation and help lay a foundation for enamel regeneration. Results: Gene expression profiles of human preameloblast and secretory ameloblast cells were obtained using human genome microarrays. From a total of 28,869 analyzed transcripts, 923 differentially expressed genes (DEGs) with FDR<0.01 and Fold-change > 2 were obtained. Among them, more than twice DEGs were found enriched in PAB (n = 647) compared with SAB (n = 276). Notably, 38 genes were identified significantly differentially expressed between PAB and SAB (Fold Change > 8). Comparison of transcriptional profiles of PAB and SAB together with KEGG pathway analysis revealed genes enrichment in PAB were chiefly involved in cell cycle control, DNA damage repair and apoptosis, while genes related to cell adhesion and extracellular matrix had elevated expression level in SAB. Two co-expression modules were further identified significantly associated with the ameloblast differentiation process by weighted gene co-expression network analysis (WGCNA).These gene networks seem to contribute to cell adhesion, tissue development, cell signaling and division. Furthermore, the co-expression associations of RunX2 and BMP8A were also observed in these modules. Conclusions: In this study, we uncovered that the differentiation from PAB to SAB may rely on a highly regulated network of interactions between conserved signal transduction pathways, including members of BMP/TGF-β, Notch, MAPK pathways to coordinate all aspects of ameloblast in intracellular processes and their social contexts. Specifically, expression of genes associated with cell cycle control, DNA damage repair, and apoptosis pathways regulates pre-ameloblast maturation during tooth development. And the SAB cells are regulated by several signaling pathways controlling enamel matrix proteins secretion and cell adhesion, which are critical for enamel formation and cell-cell interactions. Apart from showing the transcriptional patterns of PAB and SAB, the application of bioinformatic analysis also explored the potential key genes and gene-associations in ameloblast differentiation. These findings will aid in the design of new strategies to promote ameloblast functional differentiation in the regeneration and tissue engineering of teeth. Human tooth buds (18-22 weeks) were obtained from fetal cadaver tissue within 3 hours after legal abortion. Teeth were dissected from the mandibles under a laminar flow hood, embedded in OCT compound, and cryosectioned at 10-μm thickness. These sections were used for laser capture microdissection (LCM). In total of 3 pre-ameloblasts and 3 secretory ameloblasts pooled samples were used for RNA extraction and hybridization on Affymetrix microarray.
2014-10-01 | E-GEOD-59214 | biostudies-arrayexpress
Project description:Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, in addition to DNA repair, genome stability is also controlled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can alter the DNA damage cell cycle checkpoints. Here, we show that hypoxia (24h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, flow cytometric bar-coding analysis of individual cells showed that the levels of several G2 checkpoint regulators were reduced in G2 phase cells after hypoxic exposure, in particular cyclin B1. These effects were accompanied by decreased Cyclin dependent kinase (CDK) activity in G2 phase cells after hypoxia. Furthermore, cells pre-exposed to hypoxia showed a longer G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (~0.03 % O2 20h and 0.2% O2 72h). These results demonstrate that the DNA damage G2 checkpoint can be altered as a consequence of hypoxia, and we propose that such alterations may influence the genome stability of hypoxic tumors. We measured gene expression changes in U2OS cells after treatment with 0.2% hypoxia for 24 hours. The data were used in the exploration of hyopxia induced alterations in the G2 checkpoint.
2016-01-04 | E-GEOD-70530 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE27900: Gene expression analysis of mesenchymal stem cells (MSC), osteoblasts and the U2OS (osteosarcoma) cell line GSE35573: ChIP-seq analysis of H3K4Me3- and H3K27Me3-marked chromatin in mesenchymal stem cells (MSCs), osteoblasts derived from MSCs and the osteosarcoma cell line U2OS Refer to individual Series
2012-03-02 | E-GEOD-35576 | biostudies-arrayexpress
Project description:Transcriptional profiling of MSC, Osteoblasts and U2OS cells. The aim was to quantitate relative gene expression in MSC, osteoblasts and U2OS. MSC and osteoblasts were used as normal cells in this study because osteosarcoma most likely originates from MSC or osteoblasts. Cell culture and treatment: U2OS cells were cultured in McCoys 5A media (Invitrogen) containing 10% FBS. MSC and osteoblasts were cultured as described by Jaiswal et al. (J Cell Biochem 64, 295-312; 1997). Cells were treated with 5 uM 5-Azadeoxycytidine (5-Aza-CdR) or 300 nM Trischostatin-A (TSA) for 96 hours or 18 hours, respectively. Microarray analysis: Total RNA was extracted using the Qiagen kit according to the manufacturer's instructions, including a DNase step. RNA was quantified using the NanoDrop ND-100, followed by quality assessment with the 2100 Bioanalyzer (Agilent Technologies). RNA concentrations for individual samples were greater than 200ng/ul, with 28s/18s ratios greater than 2.2 and RNA integrity numbers of 10 (highest). Sample amplification and labeling procedures were carried out using the Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies) according to the manufacturer's instructions. The labeled cRNA was purified using the RNeasy mini kit (Qiagen) and quantified. RNA spike-in controls (Agilent Technologies) were added to the RNA samples before amplification. 0.75 microgram of samples labeled with Cy3 or Cy5 were mixed with control targets (Agilent Technologies), assembled on Oligo Microarray, hybridized, and processed according to the Agilent microarray protocol. Scanning was performed with the Agilent Scanner G2505B under the default settings recommended by Agilent Technologies. Data analysis: All arrays were subject to the quality checks recommended by the manufacturer. Images were visually inspected for artifacts, and distributions of signal and background intensity of both red and green channels were examined to identify anomalous arrays. No irregularities were observed, and all arrays were retained and used. All calculations were performed using the R statistical computing platform and packages from the Bioconductor bioinformatics software project. To determine the expression levels of genes in MSC, Osteoblasts and U2OS, the data were LOWESS-normalized, the probe intensities of the mock channel (no drug treatment) were extracted and set to the same scale by quantile normalization. Mean of replicate samples were calculated for each probe.
2012-03-02 | E-GEOD-27900 | biostudies-arrayexpress
Project description:Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p? 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p? 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs’ biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p? 0.0001). At FDR? 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. Tissue samples were received from the Australian Brain Donor Programs New South Wales Tissue Resource Centre, which is supported by The University of Sydney, National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism, and the New South Wales Department of Health. Cases were excluded if they had an infectious disease (i.e. HIV/AIDS, hepatitis B or C, or Creutzfeldt-Jakob disease), an unsatisfactory agonal status determined from the circumstances surrounding the death, post-mortem delays >48 hours, or significant head injury. In addition to case status, age, sex, ethnicity, brain weight, brain pH, post-mortem interval (PMI), tissue hemisphere, clinical cause of death, blood toxicology at time of death, smoking status, neuropathology and liver pathology were also provided for each subject. MiRNA and mRNA expression in 18 matched case-control pairs (N=36) with sample RINs ?6 were assessed on the Affymetrix GeneChip® Human Genome U133A 2.0 (HG-U133A 2.0) and Affymetrix GeneChip miRNA 3.0 microarray.
2015-05-22 | E-GEOD-62699 | biostudies-arrayexpress
Project description:The aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells, including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis. Experiment Overall Design: Differentiated osteoblasts (hOB) were obtained from trabecular bone fragments of four patients. hOB cultures were maintained in mineralization medium containing beta-glycerophosphate, and collected at different time points. The experimental protocol was specifically devised to mark four steps of hOB mineralization (HM). The reference sample consisted in confluent hOBs before the addition of mineralization medium (HM1).
2008-10-21 | E-GEOD-12264 | biostudies-arrayexpress
Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.
2014-06-01 | E-GEOD-51632 | biostudies-arrayexpress