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Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selective RAF inhibitors including vemurafenib (PLX4032) have demonstrated clinical efficacy in mutant BRAF driven metastatic melanoma. The clinical effectiveness of RAF inhibitors depends on near complete abolition of the MAPK pathway output in tumors harboring BRAF mutations. However these compounds paradoxically activate the MAPK pathway in cells bearing oncogenic RAS or elevated upstream receptor signaling. This paradox can promote cellular proliferation and can manifest clinically with progression of secondary malignancies such as cutaneous squamous cell carcinomas (cuSCC). We have identified next generation RAF inhibitors (paradox breakers, e.g. PLX7904) that inhibit mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation.
Publication Title
RAF inhibitors that evade paradoxical MAPK pathway activation.
Sample Metadata Fields
Specimen part, Treatment
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GSE2815- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The transcriptional activities of c-Myb and its oncogenic variant v-Myb were compared by expressing them in human MCF7 cells using recombinant adenovirus vectors. A hybrid construct, 3Mutc, which is a variant of c-Myb harboring three v-Myb-derived DNA binding domain mutations was also analyzed. All the samples were compared to cells infected with a control adenovirus. The results showed that v-Myb, which differs from c-Myb only by N- and C-terminal deletions and eleven amino acid substitutions, has a qualitatively different transcriptional activity.
Publication Title
Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptional activities of c-Myb and its oncogenic variant v-Myb were compared by expressing them in primary human monocytes using recombinant adenovirus vectors. All the samples were compared to cells infected with a control adenovirus expressing only GFP. The results showed that v-Myb, which differs from c-Myb only by N- and C-terminal deletions and eleven amino acid substitutions, has a qualitatively different transcriptional activity.
Publication Title
Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples GSE1318- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Recombinant adenovirus vectors were used to express wild type or domain swap mutants of A-Myb and c-Myb transcription factors in MCF-7 cells or pimary lung epithelial cells or fibroblasts. The results show that Myb proteins have extreme context specificity and identify sub-domains responsible for the activation of specific sets of target genes.
Publication Title
Positive and negative determinants of target gene specificity in myb transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Publication Title
Transcriptomic responses to prion disease in rats.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR < 0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR < 0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated.
Publication Title
A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 331 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 165 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series.
Publication Title
Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival.
Sample Metadata Fields
Specimen part
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