This SuperSeries is composed of the SubSeries listed below.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesE2Fs are regulators of the cell cycle and are involved in development. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesE2Fs are regulators of the cell cycle and are involved in development and hepatocellular carcinoma. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesPTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor mechanisms are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN that differentially alter the Akt axis in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation. These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients
Noncatalytic PTEN missense mutation predisposes to organ-selective cancer development in vivo.
Age, Specimen part
View SamplesPTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor roles are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation
Noncatalytic PTEN missense mutation predisposes to organ-selective cancer development in vivo.
Age, Specimen part
View SamplesThese experiments aim determine the effects of Smo and Ets-2 signaling on fibroblast gene expression.
Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.
Age, Specimen part
View SamplesThese experiments aim to determine global gene expression patterns in WT vs KPC isolated pancreatic fibroblasts Overall design: WT or KPC mice were isolated from pancreas and RNA-seq was performed
Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia.
Specimen part, Cell line, Subject
View SamplesDent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys.
Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney.
No sample metadata fields
View SamplesPurpose: Next-generation sequencing (NGS) has been utilized for systems-based analysis of all liver samples. The goals of this study were to compare the hepatic transcriptome and PBDE metabolism between conventional (CV) and germ-free (GF) mice. Methods: Livers from vehicle (corn oil), BDE-47, or BDE-99 treated adult male CV and GF mice were used for RNA-Seq (biological replicates: n=3 for CV corn oil, n=4 for CV BDE-47, n=2 for CV BDE-99, n=3 for GF corn oil, n=3 for GF BDE-47, and n=3 for BDE-99) using a HiSeq 2000 sequencer. The sequence reads that passed quality filters were mapped to the mouse reference genome (mm10) using HISAT v 0.1.6 beta; transcript abundance and differential expression were determined using Cufflinks (CuffDiff) v 2.2.1. Results: Using an optimized data analysis workflow,RNA-Seq generated approximately 47 to 68 million reads per sample, among which approximately 40 to 60 million reads were uniquely mapped to the mouse reference genome (NCBI GRCm/38/mm10). And we identified 393 drug processing genes in the livers of WT and hCAR-TG with with HISAT workflow. RNA-seq data confirmed that among all the 393 DPGs with known important functions in xenobiotic biotransformation, 90 DPGs were not expressed in livers of any groups (threshold: average FPKM < 1 in all treatment groups); whereas a total of 303 genes were expressed in livers of at least one groups, among which 258 DPGs were differentially regulated by mCAR or hCAR activation in either Day 5 or Day 60 (FDR-BH<0.05), and 45 genes were stably expressed among all treatment groups. Conclusions: Our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs, demonstrating that germ-free conditions modified the hepatic oxidation of PBDEs as well as the expression of relevant drug-processing genes in liver. Overall design: CV and GF male mice at the age of 9-weeks were treated with corn oil, BDE-47 (100umol/kg), or BDE-99 (100umol/kg) once daily for 4 consecutive days, and tissues were collected 24h after the final dose. Total RNAs were isolated from livesr using RNA zol bee reagent, and were subjected to RNA-Seq using a HiSeq 2000 sequencer.
Regulation of protein-coding gene and long noncoding RNA pairs in liver of conventional and germ-free mice following oral PBDE exposure.
Sex, Cell line, Subject
View SamplesNuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S -transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.
Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.
Sex, Age, Specimen part
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