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GSE33577
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptional profile of the human multiple myeloma (MM) cell line MM.1S treated with MLN4924 vs control MM.1S cells was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip, according to previously described protocols for total RNA extraction and purification; cDNA synthesis; in vitro transcription reaction for production of biotin-labeled cRNA; hybridization of cRNA with U133plus2.0 Affymetrix gene chips; and scanning of image output files. Scanned image output files were analyzed using DNA-Chip Analyzer (dChip) (www.dchip.org), including conversion to DCP files, normalization and modeling. The gene expression profile of MM.1S cells for each time point of MLN4924 treatment was compared to the profile of control MM.1S cells.
Publication Title
Molecular and cellular effects of NEDD8-activating enzyme inhibition in myeloma.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip.
Publication Title
Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pathologic activation of c-Myc plays a central role in pathogenesis of several neoplasias, including multiple myeloma. However, therapeutic targeting of c-Myc has remained elusive due to its lack of a clear ligand-binding domain. We therefore targeted c-Myc transcriptional function by another means, namely the disruption of chromatin-dependent signal transduction. Members of the bromodomain and extra-terminal (BET) subfamily of human bromodomain proteins (BRD2, BRD3 and BRD4) associate with acetylated chromatin and facilitate transcriptional activation by increasing the effective molarity of recruited transcriptional activators. Notably, BRD4 marks select M/G1 genes in mitotic chromatin for transcriptional memory and direct post-mitotic transcription, via direct interaction with the positive transcription elongation factor complex b (P-TEFb). Because c-Myc is known to regulate promoter-proximal pause release of Pol II, also through the recruitment of P-TEFb, we evaluated the selective small-molecule inhibitor of BET bromodomains, JQ1, as a chemical probe to interrogate the role of BET bromodomains in Myc-dependent transcription and to explore their role as therapeutic targets in c-Myc-driven neoplasias.
Publication Title
BET bromodomain inhibition as a therapeutic strategy to target c-Myc.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Publication Title
Mesenchymal stem cell features of Ewing tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Background: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Genome-wide DNA methylation patterns are established and maintained by the coordinated action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B. DNMT3B hypomorphic germline mutations are responsible for two-thirds of Immunodeficiency, Centromere Instability, Facial Anomalies (ICF) syndrome cases. The molecular defects in transcription, DNA methylation, and chromatin structure in ICF cells remain relatively uncharacterized.
Publication Title
DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
We demonstrate that Prnp dosage is critical for the maintenance of neuronal homeostasis since both its absence and, more relevantly, its overexpression induce higher sensitivity to kainate (KA) damage. These data correlate with electrophysiological results in freely behaving mutant mice showing an imbalance in activity-dependent synaptic processes, as determined from input/output curves, paired-pulse facilitation, and LTP studies. Gene expression profiling showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission among others were co-regulated in knockout and PrPc overexpressing mice. RT-qPCR analysis of neurotransmission-related genes confirmed GABA-A and AMPA-Kainate receptor subunit transcriptional co-regulation in both Prnp -/- and Tg20 mice. Our results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its interactions with GABAA and AMPA-Kainate receptors.
Publication Title
Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Serum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass. We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy. Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
Publication Title
IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival.
Publication Title
Human pancreatic cancer contains a side population expressing cancer stem cell-associated and prognostic genes.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples