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GSE2487
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
This experiment was designed to study oncogene-induced senescence (OIS). To this end we generated a series of cell lines derived from normal human diploid fibroblasts IMR90 forced to express the catalytic subunit of telomerase (hTERT). This cells were then subjected to further manipulation by orderly introducing defined genetic elements by retroviral transduction. The first cell line generated was ITV, which was obtained from the original cell line (IMR90 with hTERT) after introducing an empty vector. Subsequently, we introduced Mek:ER, which is a switchable version of the Mek kinase, a relevant downstream effector of Ras signaling during Ras-induced senescence, to generate ITM cells. We further modified this cell line by introducing SV40 small-t antigen (ST), papillomavirus oncoproteins E6 and E7 (E6/E7) or the combination of both (E6/E7 and ST). In this manner, we obtained ITMST, ITME6E7 and ITME6E7ST respectively.
Publication Title
Tumour biology: senescence in premalignant tumours.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Transcriptome of murine testis from wild type mice and mice lacking telomerase for three generations (G3-Terc), Ku86 or both telomerase and Ku86.
Publication Title
Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models.
Sample Metadata Fields
No sample metadata fields
View Samples GSE2684- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Recent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
Publication Title
Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
Sample Metadata Fields
No sample metadata fields
View Samples GSE76943- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression data from HEK293 cells expressing a doxcycline-inducible RANBP6 shRNA
Publication Title
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We used adult male Sprague-Dawley rats (280-329 g body weight). Controls were nave rats. Ischemic rats were subjected to 1-hour occlusion of the right middle cerebral artery and 16h reperfusion.
Publication Title
CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Even though much progress has been made in the understanding of the molecular nature of glioma, the survival rates of patients affected of this tumour have not changed significantly during these years. Thus, a deeper understanding of this malignancy is still needed in order to predict its outcome and improve patient treatment. Here, we report that VAV1, a GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell competition is a tumour suppressor mechanism in the thymus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes.
Publication Title
Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.
Sample Metadata Fields
Sex, Specimen part
View Samples