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GSE70262
Mus musculus
12 Downloadable Samples
Description
BACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
Publication Title
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Dysregulated Wnt signalling is seen in approximately 30% of hepatocellular cancers, thus finding pathways downstream of activation of Wnt signalling is key. Using cre lox technology we have deleted the the adenomatous polyposis coli tumour suppressor protein (Apc) within the adult mouse liver and observed a rapid increase in nuclear beta-catenin and C-Myc. This is associated with an induction of proliferation leading to hepatomegally within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes we analysed the impact of inactivating Apc in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegally phenotypes following Apc loss. However c-Myc deletion, which rescues the phenotypes of Apc loss in the intestine, had no effect on the phenotypes of Apc loss. The consequences of deregulation the Wnt pathway within the liver are therefore strikingly different to those observed within the intestine, with the vast majority of Wnt targets beta-catenin dependent but c-Myc independent in the liver.
Publication Title
B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
Description
We have performed a comprehensive transcriptional analysis of specific monocyte and macrophage (M) subsets during an acute self-resolving inflammatory insult. Following initial induction of acute inflammation, tissue resident (Resident) M are rapidly cleared from the inflammatory foci, only becoming recoverable as inflammation resolves. Monocytes are recruited to the inflammatory lesion where they differentiate into M. We term these monocyte-derived M inflammation-associated to distinguish them from Resident M which are present throughout the inflammatory response and can renew during the resolution of inflammation by proliferation. Comparative analysis of the Mo and M populations (both inflammation-associated and Resident M) identifies select genes expressed in subsets of inflammation-associated and Resident M that play important roles in the resolution of inflammation and/or for immunity, including molecules involved in antigen presentation, cell cycle and others associated with immaturity and M activation.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
HD R6/1 transgenic mouse line brain hemispheres dissected. RNA targets were created for transgenics and wildtypes at time points 18, 22 and 27 weeks. Profiles and data analysis performed using the Bioconductor software and linear model contrasts using LIMMA on RMA probeset summarys.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus, Homo sapiens
- 94 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 231 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sample Metadata Fields
Sex, Age, Disease stage, Race
View Samples- Mus musculus
- 54 Downloadable Samples
Description
The well-defined battery of in vitro systems applied within chemical cancer risk assessment is often characterised by a high false-positive rate, thus repeatedly failing to correctly predict the in vivo genotoxic and carcinogenic properties of test compounds. Toxicogenomics, i.e. mRNA-profiling, has been proven successful in improving the prediction of genotoxicity in vivo and the understanding of underlying mechanisms. Recently, microRNAs have been discovered as post-transcriptional regulators of mRNAs. It is thus hypothesised that using microRNA response-patterns may further improve current prediction methods. This study aimed at predicting genotoxicity and non-genotoxic carcinogenicity in vivo, by comparing microRNA- and mRNA-based profiles, using a frequently applied in vitro liver model and exposing this to a range of well-chosen prototypical carcinogens. Primary mouse hepatocytes (PMH) were treated for 24 and 48h with 21 chemical compounds [genotoxins (GTX) vs. non-genotoxins (NGTX) and non-genotoxic carcinogens (NGTX-C) versus non-carcinogens (NC)]. MicroRNA and mRNA expression changes were analysed by means of Exiqon and Affymetrix microarray-platforms, respectively. Classification was performed by using Prediction Analysis for Microarrays (PAM). Compounds were randomly assigned to training and validation sets (repeated 10 times). Before prediction analysis, pre-selection of microRNAs and mRNAs was performed by using a leave-one-out t-test. No microRNAs could be identified that accurately predicted genotoxicity or non-genotoxic carcinogenicity in vivo. However, mRNAs could be detected which appeared reliable in predicting genotoxicity in vivo after 24h (7 genes) and 48h (2 genes) of exposure (accuracy: 90% and 93%, sensitivity: 65% and 75%, specificity: 100% and 100%). Tributylinoxide and para-Cresidine were misclassified. Also, mRNAs were identified capable of classifying NGTX-C after 24h (5 genes) as well as after 48h (3 genes) of treatment (accuracy: 78% and 88%, sensitivity: 83% and 83%, specificity: 75% and 93%). Wy-14,643, phenobarbital and ampicillin trihydrate were misclassified. We conclude that genotoxicity and non-genotoxic carcinogenicity probably cannot be accurately predicted based on microRNA profiles. Overall, transcript-based prediction analyses appeared to clearly outperform microRNA-based analyses.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus
- 57 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus
- 106 Downloadable Samples
Description
Specification of germ cell fate is fundamental in development. With a highly representative single-cell microarray and rigorous quantitative-PCR analysis, we defined the genome-wide transcription dynamics that create primordial germ cells (PGCs) from the epiblast, a process that exclusively segregates them from their somatic neighbors. We also analyzed the effect of the loss of Blimp1, a key transcriptional regulator, on these dynamics. Our analysis revealed that PGC specification involves complex, yet highly ordered regulation of a large number of genes, proceeding under the strong influence of mesoderm induction with active repression of specific programs such as epithelial-mesenchymal transition, Hox gene activation, cell-cycle progression and DNA methyltransferase machinery. Remarkably, Blimp1 is essential for repressing nearly all the genes normally down-regulated in PGCs relative to their somatic neighbors, whereas it is dispensable for the activation of approximately half of the genes up-regulated in PGCs.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
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