Differential gene expression in Gaddβ KO mice treated with diethylnitrosamine and phenobarbital
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE231793 | GEO | 2023/09/25
REPOSITORIES: GEO
Similar Datasets
Project description:Differential gene expression in Gaddβ KO mice treated with diethylnitrosamine and phenobarbital
| PRJNA967695 | ENA
Project description:In rodent liver, a single injection of N-nitrosodiethylamine (DEN) followed by chronic treatment with the antiepileptic drug phenobarbital (PB) promotes the outgrowth of hepatocellular tumors with activating mutations in Ctnnb1, encoding the transcription factor β-catenin. We now studied long-term effects of PB treatment in livers of transgenic mice with hepatocyte-specific knockout (KO) of Apc, a negative regulator of β-catenin signaling. The number of Apc KO hepatocytes present in the liver decreased with age, indicative of a selective disadvantage of Apc KO cells in the absence of PB. Following liver tumor promotion by PB in Apc KO mice for 9 months, tumor burden was quantified and histological appearance, gene expression profiles, and activity of oncogenic signaling pathways of the tumors were analyzed. In Apc KO mice fed with PB, we observed an increased hepatic tumor volume fraction and tumor multiplicity, as compared to non-promoted animals. Tumors in the PB-treated Apc KO group were mostly eosinophilic hepatocellular adenoma with activated β-catenin, due to the deletion of Apc. These tumors exhibited striking phenotypic similarities to DEN-induced Ctnnb1-mutated tumors, regarding histological appearance and expression of marker proteins and mRNAs. A particular sub-population of tumors, Apc KO-driven basophilic hepatocellular carcinomas, exclusively appeared in the non-PB-treated group but was absent from PB-promoted livers. In conclusion, phenobarbital promotes the outgrowth of Apc-deficient, β-catenin-activated hepatocellular adenoma while simultaneously inhibiting the formation of a certain population of Apc-driven hepatocellular carcinoma.
2018-05-17 | GSE68969 | GEO
Project description:Effect of phenobarbital on Sf9 cell cultures genes expression. RNA from phenobarbital treated Sf9 cell cultures were compared to control treated (DMSO) Sf9 cell
2018-09-22 | GSE32337 | GEO
Project description:Gene-expression profiles of rat hepatocellular carcinoma induced by diethylnitrosamine (DEN) and the effect of erlotinib Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. Given the lack of successful treatment options, chemoprevention in high-risk patients has been proposed as an alternative strategy. Mounting evidence supports a role for epidermal growth factor (EGF) during chronic liver disease and hepatocellular transformation. We address the hypothesis that blocking the EGF-EGF receptor (EGFR) pathway may be an effective strategy for inhibiting fibrogenesis and hepatocarcinogenesis. A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the effects of erlotinib on underlying chronic liver disease and HCC formation. The DEN-induced rat model closely resembles disease progression in humans both pathologically and molecularly. Erlotinib significantly prevented the development of HCC tumor nodules in a dose-dependent fashion. Further, erlotinib inhibited the activation of hepatic stellate cells and prevented fibrogenesis. Erlotinib also reduced hepatotoxicity and improved liver function. Finally, a gene expression signature predictive of poor survival in human cirrhosis patients was reversed in response to erlotinib. Our data demonstrate for the first time that EGFR inhibition prevents liver fibrogenesis. Further, our results suggest that erlotinib is a potentially effective HCC chemoprevention strategy through inhibition of cirrhosis progression which can be monitored at the molecular level.
2014-02-28 | GSE27638 | GEO
Project description:Drug addiction is a chronic relapsing brain disease. The alterations of glucose uptake and metabolism were found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Here, we established a rat model of phenobarbital addiction by 90 days dosed escalation and evaluated addiction-related symptoms. We also performed proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by LC-MS/MS on day 60 and 90 of phenobarbital or 0,5% CMC-Na (vehicle) administration. The results showed that phenobarbital addictive rats developed severe withdrawal symptoms after abstinence. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration; which CALM1, ARAF and Cbl proteins (related to insulin signaling pathway) were significantly downregulated on day 60 but no day 90; however, SLC27A3 and NF-kB1 proteins (related to insulin resistance) were significantly upregulated on day 90. Our data indicate that insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury and the findings may have important clinical implication.
2020-10-29 | PXD021101 | Pride
Project description:Through the analysis of mouse liver tumours promoted by distinct routes (DEN exposure alone, DEN exposure plus non-genotoxic insult with phenobarbital and non-alcoholic fatty liver disease); we report that the cancer associated hyper-methylated CGI events in mice are also predicated by silent promoters that are enriched for both the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone modification H3K27me3 in normal liver. During cancer progression these CGIs undergo hypo-hydroxymethylation, prior to subsequent hyper-methylation; whilst retaining H3K27me3. A similar loss of promoter-core 5hmC is observed in Tet1 deficient mouse livers indicating that reduced Tet1 binding at CGIs may be responsible for the epigenetic dysregulation observed during hepatocarcinogenesis. Consistent with this reduced Tet1 protein levels are observed in mouse liver tumour lesions. As in human, DNA methylation changes at CGIs do not appear to be direct drivers of hepatocellular carcinoma progression in mice. Instead dynamic changes in H3K27me3 promoter deposition are strongly associated with tumour-specific activation and repression of transcription. Our data suggests that loss of promoter associated 5hmC in diverse liver tumours licences DNA methylation reprogramming at silent CGIs during cancer progression. We carry out paired end , strand specific RNAseq prior to sequencing on Illumina Hiseq 2500 to report on the transcriptional landscape in replicate control mouse livers (n=2), 12 week Phenobarbital exposed livers (n=2)and resulting (35 week PB) liver tumours (n=3).
2016-05-17 | E-GEOD-77729 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with phenobarbital treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (300 uM and 3 mM) of phenobarbital and water vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis.
2012-08-28 | GSE40339 | GEO
Project description:Phase I trial to study the effectiveness of irinotecan plus cyclosporine and phenobarbital in treating patients who have solid tumors or lymphoma that is refractory to standard therapy. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Cyclosporine and phenobarbital may enhance the effectiveness of irinotecan.
| 2002394 | ecrin-mdr-crc
Project description:In primary human hepatocytes (PHH) the involvement of the Pregnane X Receptor (PXR) in genes regulations by Phenobarbital (PB) has never been evaluated at the transcriptomic level. Here we investigated the impact of PXR depletion and epidermal growth factor on PXR dependent gene modulation by PB in PHH. The potential crosstalk with CAR was investigated using Phenobarbital and the direct CAR activator (CITCO) in presence or in absence of EGF.
2018-04-27 | GSE68495 | GEO
Project description:The drug phenobarbital induces cytochrome P450 monooxygenase (P450) gene expression in many animals, but no changes in P450 expression, or expression of any detoxification genes, were observed in worker honey bees fed on phenobarbital-candy relative to bees fed plain candy. Keywords: Expression profiling by array
2012-05-12 | GSE34029 | GEO