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Mus musculus
93 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimers disease, as well as cancer.
Publication Title
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems (T3SSs), encoded in pathogenicity islands 1 (SPI1) and 2 (SPI2), respectively. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with certain host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both T3SSs. Nothing is known about the function of this protein inside the host cells. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in epithelial cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also represses genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. Consisted with this analysis a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, reduction of cytotoxicity, cell-cell adhesion and migration capability, and increase in endocytosis.
Publication Title
Global impact of Salmonella type III secretion effector SteA on host cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 m2/cm2 dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 h. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 h and 205 genes at 24 h, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 h. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 h and no changes at 24 h, whereas expression levels of 30 genes were elevated at 8 h at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of 2 genes (NR4A2, MIP2) at 8 h and 16 genes at 24 h that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells.
Publication Title
Alterations in gene expression in human mesothelial cells correlate with mineral pathogenicity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Sus scrofa
- 208 Downloadable Samples
Illumina HiSeq 2500
Description
we report single cell expression profiles of embryonic cells (from day 5 to 11) of pig embryo development. Overall design: single cell transcriptomes were generated from 220 cells obtained from 28 embryos (15 male and 13 female)
Publication Title
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE1559- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
HSC (Sca+ SP) were isolated from 8-12 week C57B6 mice at various time points after treatment with 5-Fluorouracil. RNA was isolated from 50,000-100,000 FACS sorted cells and subjected to two rounds of T7 based linear amplification using Ambion's Message Amp kit. Two replicates from each time point were analyzed.
Publication Title
Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Anopheles gambiae
- 4 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
In the present study, we have investigated the effect of CpG Oligodeoxynucleotides (CpG-ODN) on the outcome of Plasmodium infection of the mosquito vectors Anopheles stephensi and Anopheles gambiae and on the modulation of mosquito immunity to Plasmodium. Anopheles mosquitoes inoculated with CpG-ODN showed significant reduction of Plasmodium infection rate and intensity. Microarrays were used to profile transcription of fat-body from CpG-ODN-treated mosquitoes. Mosquitoes were dissected 18h after ODN inoculation (immediately before feeding). Batches of 20 to 30 fat bodies (abdomen without midgut, ovaries and malpighian tubule]) were dissected in cold DEPC-treated phosphate-buffered saline (PBS) and processed for RNA preparation. Mosquitoes treated with CpG-ODNs are less susceptible to Plasmodium infection. Transcription profile of fat body indicates that protection was associated with coagulation/wound healing, while melanization appears to be depressed.
Publication Title
CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rß). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients. Overall design: Wild-type MCF-7 cells were treated with vehicle control (0.1% ethanol), E2 (10-9 mol/L) and 4-OHT (10-6 mol/L) respectively for 24 hours.
Publication Title
Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 912 Downloadable Samples
- Illumina HiSeq 2500
Description
Genetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples
Publication Title
Identification of potential therapeutic targets in prostate cancer through a cross-species approach.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In prostate cancer, the androgen receptor (AR) is a key transcription factor at all disease stages. We recently showed that during progression to castrate-resistant prostate cancer the AR acquires the ability to bind to a distinct set of genomic sites in tissue samples and that some of the genes that are regulated by the AR in these conditions correlate with poor prognosis. Based on this work we hypothesised that the AR is reprogrammed through interactions with other transcription factors. In the present study we show that GABP, an ETS transcription factor which is upregulated in CRPC, is an AR-interacting transcription factor. Ectopic expression of GABPA in prostate cancer cell-lines enables them to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes.
Publication Title
The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples