Mouse keratinocytes were isolated from K15-EGFP transgenic mice for FACS sorting. RNA samples from EGFP-high and alpha-6 integrin positive cells (hair follicle stem cells) and from EGFP negative and alpha-6 integrin positive cells were used for Microarray analysis.
Capturing and profiling adult hair follicle stem cells.
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Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesThe carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View SamplesConventional notion regards the action of non-genotoxic carcinogens (NGC) an autonomous process largely confined to parenchymal cells. Here we aim to elucidate the role of the hepatic mesenchyme for the action of two prototypical NGC, phenobarbital (PB), an anti-epileptic drug, and cyproterone acetate (CPA) a gestagen used in contraceptive pills.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment
View SamplesHere we investigate the difference in global gene expression in different tumor types found in the liver of rats after NNM-initiation/PB-promotion of tumor growth. We aim to identify tumor characteristic expression in nodules, focii, adenomas and carcinomas.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment
View SamplesEvidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View SamplesSignaling through the Wnt/b-catenin pathway is a crucial determinant of hepatic zonal gene expression, liver development, regeneration, and tumorigenesis. The gene encoding b-catenin is called Ctnnb1. We have previously shown, that liver tumour promotion mediated by the model tumour promoter phenobarbital (PB) is completely lost in mice, where Ctnnb1 has been conditionally knocked out in hepatocytes (CTNNB1KO mice; Rignall et al., Carcinogenesis 32, 52-57, 2010). In the present study, the effect of a 12 weeks PB exposure on the liver miRNA expression pattern was investigated, in order to potentially get information on the nature of the loss of promotional activity in the CTNNB1KO mice.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part
View SamplesConventional notion regards the action of non-genotoxic carcinogens (NGC) an autonomous process largely confined to parenchymal cells. Here we aim to elucidate the role of the hepatic mesenchyme for the action of a prototypical NGC, phenobarbital (PB), an anti-epileptic drug.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Specimen part, Treatment
View SamplesCurrently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy.
Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
Specimen part
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