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GSE41296
Homo sapiens
120 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. This approach has been shown to differentiate between DNA reactive genotoxins and non-DNA reactive or indirectly-acting genotoxins. In this context, it has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known to be a DNA-reactive substance which mainly induces chromosomal damage in cultured mammalian cells. However, there has been concern that FA might also act as an aneugen (i.e., induce aneuploidy) but recent cytogenetic studies did not support this assumption. To further characterize FA's genotoxic mode of action, we now used gene expression profiling as a molecular tool to differentiate between clastogenic and aneugenic activity. TK6 cells were exposed to FA for 4 and 24 h and changes in gene expression were analyzed using a whole-genome human microarray. Results were compared to the expression profiles of two DNA-damaging clastogens (methyl methanesulfonate [MMS] and ethyl methanesulfonate [EMS]) and two aneugens (colcemid [COL] and vincristine [VCR]). The gene expression profiles indicated that clastogens and aneugens induce discriminable gene expression patterns. The expression profile of FA showed more similarities to clastogens than to aneugens. Hierarchical clustering analysis as well as several class prediction algorithms revealed a much closer relationship of FA with clastogens than with aneugens. A pathway analysis of differentially regulated genes also demonstrated an overall better agreement of FA with clastogens than with aneugens. Altogether, the results of this study revealed great similarities in gene expression in response to FA and clastogens but did not support an aneugenic activity of FA.
Publication Title
Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Bos taurus
- 16 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Steer liver transcriptome
Publication Title
Differential expression of genes related to gain and intake in the liver of beef cattle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Bos taurus
- 16 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Steer spleen transcriptome
Publication Title
Profile of the Spleen Transcriptome in Beef Steers with Variation in Gain and Feed Intake.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 15 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Steer mesenteric fat transcriptome.
Publication Title
Relationships between the genes expressed in the mesenteric adipose tissue of beef cattle and feed intake and gain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Central corneal thickness (CCT) exhibits broad variability. We determined the corneal gene expression profile three mouse strains with distinct corneal thickness: C57BLKS/J (88.6 um), SJL/J (123.5 um), and C57BL/6J (100.1 um).
Publication Title
Genetic dependence of central corneal thickness among inbred strains of mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 47 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Steer small intestine transcriptome
Publication Title
Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mast cells, activated by antigen via the high affinity receptor for IgE (FcRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
Publication Title
Stem cell factor programs the mast cell activation phenotype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Bos taurus
- 16 Downloadable Samples
Illumina Genome Analyzer II
Description
RNA sequencing (RNA-Seq) was performed on rumen papillae from 16 steers with variation in gain and feed intake. Overall design: Sixteen rumen papillae samples were sequenced by Cofactor Genomics (St.Louis, MO).
Publication Title
Transcriptome differences in the rumen of beef steers with variation in feed intake and gain.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Lineage plasticity is a major mechanism driving prostate cancer progression and antiandrogen therapy resistance. Deletions or mutations in phosphatase and tensin homolog (PTEN) and TP53 tumor suppressor genes have been linked to lineage plasticity in prostate cancer. Fusion-driven overexpression of the E-twenty-six transformation specific (ETS)-related gene (ERG), encoding an oncogenic transcription factor, is observed in approximately 50% of all prostate cancers, yet its role in prostate cell lineage determination remains elusive. Here we demonstrate that transgenic expression of prostate cancer-associated ERG blocks Pten and Trp53 mutation-induced decreased expression of Ar and its downstream target genes and loss of luminal epithelial cell identity in the mouse prostate. Integrative analyses of ERG chromatin-immunoprecipitation sequencing (ChIP-seq) and transcriptome data show that ERG suppresses expression of a subset of cell cycle-promoting genes and RB phosphorylation, which in turn causes repression of E2F1-mediated expression of non-epithelial lineage genes. Xenograft studies show that PTEN/TP53 double mutated prostate tumors are responsive to the cyclin-dependent kinase 4 or 6 (CDK4/6) inhibitor palbociclib, but resistant to the AR inhibitor enzalutamide, while ERG/PTEN/TP53 triple-mutated prostate tumors behave completely opposite. Our studies identify ERG and the repressed cell cycle gene signature as intrinsic inhibitors of PTEN/TP53 double mutation-elicited lineage plasticity in prostate cancer. Our findings also suggest that ERG fusion can be utilized as a biomarker to guide the treatment of PTEN/TP53-mutated, RB1-intact prostate cancer with either antiandrogen or anti-CDK4/6 therapies. Overall design: Prostate tissue from mice with 1) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity, or 2) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity and transgenic ERG expression were harvested at 4-5 months. RNA was isolated from tissue and RNA-seq experiments were then performed for both genotype samples in triplicates. Differentially expressed genes were identified by comparing genotype #1 and genotype #2.
Publication Title
<i>TMPRSS2-ERG</i> Controls Luminal Epithelial Lineage and Antiandrogen Sensitivity in <i>PTEN</i> and <i>TP53</i>-Mutated Prostate Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations involving the NFKB pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCL). These mutations, which are thought to be progression events, enable MM tumors to become less dependent on extrinsic bone marrow signals that activate NFKB. Studies on a panel of 50 MMCL provide some clarification of the mechanisms through which these mutations act and the significance of classical vs alternative activation of NFKB. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, TACI) selectively activate the classical pathway. However, most mutations affecting NIK level (NIK, TRAF2, TRAF3, cIAP1&2, CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteosomal degradation of NIK in MM.
Publication Title
Classical and/or alternative NF-kappaB pathway activation in multiple myeloma.
Sample Metadata Fields
Cell line
View Samples