Glioblastoma multiforme (GBM) is a highly malignant primary central nervous neoplasm characterized by tumor cell invasion, robust angiogenesis, and a mean survival of 15 months. Human cytomegalovirus (HCMV) infection is present in > 90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear. We report here that a majority of human GBM tumors express HCMV pp71, which has previously been found to promote cell cycle progression and viral replication, and that pp71 is expressed preferentially within the CD133+ cancer stem cell-like subpopulation. Overexpression of pp71 in adult neural precursor cells (NPCs) resulted in a dramatic induction of stem cell factor (SCF) gene expression, which has been identified as an important pro-angiogenic factor in GBM.
Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor.
Cell line
View SamplesPrimary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.
Specimen part, Disease stage
View SamplesNovel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006.
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
Sex, Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesWe introduced the HCMV IE1 gene into a mouse model of spontaneous glioma driven by p53KD and overexpression of Ras and PDGF and compared the transcriptomes of mouse gliomas +/- IE1. The following plasmids were utilized for glioma induction in equal parts: pT2/C-Luc/PGK-SB100, pT2/Cag-NrasV12, pT2/shP53/GFP4/mPDGF, and pT2/Cag-IE1 or pT2/C-Neo.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesPrimary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes)
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesHeterochromatic non-coding RNAs induce breast tumor formation in mice by interacting with BRCA1-associated proteins functioning in the DNA damage response. Overall design: mouse tumor mRNA profiles using ribosomal mRNA depletion
Heterochromatin-Encoded Satellite RNAs Induce Breast Cancer.
Specimen part, Cell line, Subject
View SamplesBackground: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sex
View SamplesYB-1 controls epithelial-mesenchymal transitions by restricting translation of growth-related mRNAs and enabling expression of EMT-inducing transcription factors. We used microarrays to characterize the direct transcriptional and indirect translational regulation of mRNAs by exogenous YB-1 in breast cancer cell lines.
Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
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View SamplesTmprss6 is the master inhibitor of hepcidin and its inactivation causes iron refractory iron deficiency anemia both in human and in mice. Mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficienct-high hepcidin Tmprss6 null mice. We investigated the transcriptional response associated with chronic hepcidin overexpression by comparing whole genome transcription profiling of the liver of Tmprss6 KO mice and IDA animals, irrespective of iron deficiency.
A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.
Age, Specimen part
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