Purpose: We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model of breast cancer that closely recapitulates human breast cancer. This report makes these data publicly available in raw and processed forms, as a resource to the community. Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens.
Proteome and transcriptome profiles of a Her2/Neu-driven mouse model of breast cancer.
Sex, Specimen part
View SamplesMethyl tert-butyl ether (MTBE) has been shown to target developing vasculature in piscine and mammalian model systems. In the zebrafish, MTBE induces vascular lesions throughout development. These lesions result from exposure to MTBE at an early stage in development (6-somites to Prim-5 stages). During this time period, transcript levels of vegfa, vegfc, and vegfr1 were significantly decreased in embryos exposed to 5 mM MTBE.
Manipulation of the HIF-Vegf pathway rescues methyl tert-butyl ether (MTBE)-induced vascular lesions.
Specimen part
View SamplesAstrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown. To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response. Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated. To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology. Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO. In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days. Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity. To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used. Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke. In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO. Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia.
Effects of heat shock protein 72 (Hsp72) on evolution of astrocyte activation following stroke in the mouse.
Sex, Treatment
View SamplesSV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used enterocytes from the mouse small intestine expressing TAg. Expression of TAg in the mouse intestine results in hyperplasia and dysplasia. Our analysis indicates that practically all gene expression regulated by TAg in enterocytes is dependent upon its binding and inactivation of the Rb-family proteins.
Simian virus 40 T-antigen-mediated gene regulation in enterocytes is controlled primarily by the Rb-E2F pathway.
Sex, Age, Specimen part
View SamplesThe presence of unspliced transcripts in hematopoietic stem cells (HSCs) and the proposed association of CREBBP with the constitutive production of unspliced RNA and with pre-mRNA processing prompted us to examine more closely an anomaly we had noted in microarray-based gene expression studies but had previously attributed to experimental noise. We noticed that more than half of the probe sets down-regulated in Crebbp+/- fetal liver HSCs (FLHSCs) relative to wild-type (WT) mapped entirely within introns, rather than detecting exonic or spliced sequences. We therefore set out to test whether this might be evidence that reduced CREBBP levels selectively alter the generation of full-length, unspliced pre-mRNA. We also asked whether this process might be associated with differentiation since self-renewal and lineage commitment are the both responses for which HSCs are primed.
Inactivation of a single copy of Crebbp selectively alters pre-mRNA processing in mouse hematopoietic stem cells.
Specimen part
View SamplesBackground: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids.
Activation of sterol-response element-binding proteins (SREBP) in alveolar type II cells enhances lipogenesis causing pulmonary lipotoxicity.
Specimen part
View SamplesCumulus-oocyte complexes were isolated a seperate time-points to generate temporal complexes. Targets from two biological replicates at each time point (0h, 8h, 16h post-hCG treatment) were generated and the expression profiles were determined using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Comparisons between the sample groups allow the identification of genes with temporal expression patterns.
Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process?
No sample metadata fields
View SamplesDeletion of the gene encoding Foxa2, a winged helix transcription factor selectively expressed in respiratory epithelial cells, caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia. Loss of Foxa2 induced the recruitment and activation of myeloid dendritic cells (mDCs) and Th2 cells in the lung, and was associated with the increased production of T helper 2 (Th2) cytokines and chemokines. mRNA microarray analysis demonstrated that deletion of Foxa2 induced the expression of a number of mRNAs regulating pulmonary dendritic cell activation, Th2 mediated inflammation, and goblet cell differentiation. The spontaneous pulmonary inflammation and goblet cell metaplasia caused by loss of Foxa2 was inhibited by treatment of newborn Foxa2/ mice with monoclonal IL-4Ralpha antibody. Expression of Foxa2 in non-ciliated secretory cells (Clara cells) in vivo inhibited goblet cell differentiation induced by pulmonary allergen exposure. The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2.
Foxa2 programs Th2 cell-mediated innate immunity in the developing lung.
Specimen part
View SamplesThe molecular targets of SRC-2 regulation in the murine liver stimulate fatty acid degradation and glycolytic pathway while fatty acid, cholesterol, and steroid biosynthetic pathways are down-regulated.
The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism.
Sex, Specimen part
View SamplesMost tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
No sample metadata fields
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