Expression profile of Pten loss and ERG overexpression in mouse prostate
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46799 | GEO | 2013/05/10
SECONDARY ACCESSION(S): PRJNA202377
REPOSITORIES: GEO
Similar Datasets
Project description:We performed expression mouse profiling of prostates of 3 month WT, ERG, PTEN f/f and Pten f/f;ERG mice. For WT and ERG prostates, entire prostates were dissected and total RNA immediated harvested. For Pten f/f and Pten f/f;ERG prostates, the Ventral Lobe was dissected. Mice are in the C57B6 background. The prostate were harvested and RNA isolated by standard protocols and analyzed by expression profiling.
2013-05-10 | E-GEOD-46799 | biostudies-arrayexpress
Project description:We performed expression mouse profiling of prostates of 3 month PTEN f/f and Pten f/f;R26(ERG) mice and assessed the response to 3 days of castration.
2013-04-25 | GSE46360 | GEO
Project description:We performed expression mouse profiling of prostates of 3 month PTEN f/f and Pten f/f;R26(ERG) mice and assessed the response to 3 days of castration. Mice are in the C57B6 background. Two mice in each group were castrated. Three days after castration, the prostate were harvested and RNA isolated by standard protocols and analyzed by expression profiling.
2013-04-25 | E-GEOD-46360 | biostudies-arrayexpress
Project description:Translocation of ETS transcription factors including ERG and ETV1 occur in half of all prostate cancers. We generated a mouse model of ERG ovexpression (Rosa26-ERG) which when crossed into prostate specific probasin-Cre, expressed ERG specifically in the prostate. We crossed Rosa26-ERG into Pten flox/flox allele to generate compound GEMM mouse. Here, we determined the genomic binding sites of ERG, AR, and the histone marks H3K4me1 and H3K4me3 that maps enhancers and promoters respectively in the prostates of these mice.
2013-06-13 | GSE47119 | GEO
Project description:Translocation of ETS transcription factors including ERG and ETV1 occur in half of all prostate cancers. We generated a mouse model of ERG ovexpression (Rosa26-ERG) which when crossed into prostate specific probasin-Cre, expressed ERG specifically in the prostate. We crossed Rosa26-ERG into Pten flox/flox allele to generate compound GEMM mouse. Here, we determined the genomic binding sites of ERG, AR, and the histone marks H3K4me1 and H3K4me3 that maps enhancers and promoters respectively in the prostates of these mice. The prostate of four six month old mice of each genotype were pooled. The chromatin was isolated and ChIP-Seq performed.
2013-06-13 | E-GEOD-47119 | biostudies-arrayexpress
Project description:The current study defines the how ERG, PTEN, and AR inteact to regulate the transciptome in established prostate cancers. Prostate cancer organoids were derived from established prostate cancer in GEM models harboring ERG over-expression and/or loss of PTEN and cultured in vitro using prostate epithelial organoid culture conditions. The established organoids were then isolated as individual clones in triplicate and CRISPR strategies were employeed to knock out ERG and AR. RNA was isolated under physiologic steady state growth conditions and 24 hour treatment with the AR inhbitor MDV3100 in a subset of ERG-PTEN CRISPR ERG organoids.
2018-03-29 | GSE112469 | GEO
Project description:Lineage plasticity is a major mechanism driving prostate cancer progression and antiandrogen therapy resistance. Deletions or mutations in phosphatase and tensin homolog (PTEN) and TP53 tumor suppressor genes have been linked to lineage plasticity in prostate cancer. Fusion-driven overexpression of the E-twenty-six transformation specific (ETS)-related gene (ERG), encoding an oncogenic transcription factor, is observed in approximately 50% of all prostate cancers, yet its role in prostate cell lineage determination remains elusive. Here we demonstrate that transgenic expression of prostate cancer-associated ERG blocks Pten and Trp53 mutation-induced decreased expression of Ar and its downstream target genes and loss of luminal epithelial cell identity in the mouse prostate. Integrative analyses of ERG chromatin-immunoprecipitation sequencing (ChIP-seq) and transcriptome data show that ERG suppresses expression of a subset of cell cycle-promoting genes and RB phosphorylation, which in turn causes repression of E2F1-mediated expression of non-epithelial lineage genes. Xenograft studies show that PTEN/TP53 double mutated prostate tumors are responsive to the cyclin-dependent kinase 4 or 6 (CDK4/6) inhibitor palbociclib, but resistant to the AR inhibitor enzalutamide, while ERG/PTEN/TP53 triple-mutated prostate tumors behave completely opposite. Our studies identify ERG and the repressed cell cycle gene signature as intrinsic inhibitors of PTEN/TP53 double mutation-elicited lineage plasticity in prostate cancer. Our findings also suggest that ERG fusion can be utilized as a biomarker to guide the treatment of PTEN/TP53-mutated, RB1-intact prostate cancer with either antiandrogen or anti-CDK4/6 therapies.
2018-05-16 | GSE103871 | GEO
Project description:TMPRSS2-ERG gene fusions that are frequently identified in prostate cancer can be generated either through chromosomal translocation or via interstitial deletion. The latter mechanism deletes an interstitial region of ~3Mb and it remains largely unanswered whether genes deleted within this region contribute to prostate cancer. By characterizing two knockin mouse models recapitulating TMPRSS2-ERG fusions with or without the interstitial deletion, we found that only those with deletion developed poorly differentiated adenocarcinomas with epithelial-to-mesenchymal transition, when under a Pten-null background. We identified several interstitial genes, including ETS2 and BACE2, whose reduced expression correlates with worse disease-free survival and lethal disease. By using an Ets2 conditional knockout allele, we demonstrated that loss of one copy of Ets2 was sufficient for prostate cancer progression when under a Pten-null background. Collectively, our data suggest that ETS2 is a prostate tumor suppressor and haploinsufficiency of one or more interstitial genes contributes to prostate cancer progression. Genotyped male mice were euthanized at 12 months of age and prostates isolated. Prostates were fixed overnight in 10% formalin and stored in 70% ethanol until tissue processing and paraffin embedding. Serial sections were cut from paraffin blocks which were stained for H&E and analyzed by a trained rodent histopathologist. Using these sections as a visual guide for specific types of lesions, the sequential sections were stained with hematoxylin and used for laser capture microdissection on ArcturusXT system. Epithelial cells within notable high grade prostate intraepithelial neoplasia (HG-PIN) lesions were microdissected from 3 mice from each corresponding genotype. In addition, poorly differentiated adenocarcinomas from PbCre;T-3Mb-Erg/+;PtenL/L mice were also dissected. RNA was isolated from the microdissected tissue using the Qiagen RNeasy FFPE kit and subjected to Nugen Amplification before microarray analysis on an Affymetrix Mouse Gene 2.0 ST chip.
2015-12-31 | E-GEOD-63070 | biostudies-arrayexpress
Project description:To determine if ERG expression and PTEN loss were sufficient to transform prostate epithelial cells we constructed cell lines with expression of the TMPRSS2/ERG fusion gene (TE), stable knockdown of PTEN with shRNA (PTEN KD) or both alterations (PTEN KD/TE) using the PNT1A cell line. To determine what gene expression changes are associated the phenotypic changes between the cell line experimental groups, we carried expression microarray studies using Agilent 60K expression microarrays. RNAs from all four cell lines were analyzed in duplicate and probes with ≥ 1.4-fold or ≤0.7-fold relative to control cells identified. Our results demonstrated that PTEN loss and expression of the TMPRSS2/ERG fusion gene transform prostatic epithelial cells via enhanced FGF signaling.
2018-04-04 | GSE101635 | GEO
Project description:We used microarrays to analyze the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Pb-Cre4;PtenLoxP/LoxP anterior prostates, Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostates at 12 weeks of age. Prostate-specific Pten deletion (Pb-Cre4;PtenLoxP/LoxP) results in prostate intraepithelial neoplasia (PIN) which, following a long latency, can progress to high-grade adenocarcinoma, albeit with minimally invasive and metastatic features. However, inactivation of Lrf in the prostate epithelium in combination of Pten results in aggressive prostate tumors. To understand the molecular mechanisms by which loss of Lrf promotes Pten-loss-driven prostate tumorigenesis, we conducted transcriptome comparison of three wild-type anterior prostates, three Pb-Cre4;PtenLoxP/LoxP PIN, and three Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostate tumors.
2013-05-19 | E-GEOD-46473 | biostudies-arrayexpress