Genome-wide Profiling of SRC-2 (NCOA2) binding in mouse prostate [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54770 | GEO | 2014/06/30
SECONDARY ACCESSION(S): PRJNA237587
REPOSITORIES: GEO
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Project description:Using genetically engineered mice, overexpressing SRC-2, specifically in the prostate epithelium of PTEN heterozygous mice accelerates PTEN mutation induce tumor progression and develops a metastasis-prone cancer. Here we used ChIP-Seq analysis to identify genome-wide SRC-2 binding sites in mouse prostate. Examination of genome-wide SRC-2 binding in mouse prostate by ChIP-seq analysis. Samples were collected from pooled dorsal-lateral prostates of 7 months old-PTEN flox/+; Rosa26-SRC-2 OE/+ mice. Flash frozen tissues were then sent to Active Motif, Inc. for chromatin extraction and followed by immunoprecipitation using anti-SRC-2 antibody (A300-346A, Bethyl Lab., Inc.).
2014-06-30 | E-GEOD-54770 | biostudies-arrayexpress
Project description:SRC-2 is frequently amplified or overexpressed in metastatic prostate cancer patients. In this study, we used genetically engineered mice, overexpressing SRC-2 specifically in the prostate epithelium as a mouse model to examine the role of SRC-2 in prostate tumorigenesis. Over-expression of SRC-2 in PTEN heterozygous mice accelerates PTEN mutation induced tumor progression and develops a metastasis-prone cancer. We used microarrays to examine the molecular profile of prostate-specific SRC-2 overexpression adult dorsal-lateral prostate in comparison with that of control PTENF/+ heterozygous deletion mice. Total RNA was extracted from dorsal-lateral prostate of 7 months old-PTEN flox/+ control and PTEN flox/+; Rosa26-SRC-2 OE/+ adult mice, followed by gene expression profiling using Affymetrix microarrays. Each sample contains pooled prostate RNA from 3 mice.
2014-06-30 | E-GEOD-54678 | biostudies-arrayexpress
Project description:SRC-2 is frequently amplified or overexpressed in metastatic prostate cancer patients. In this study, we used genetically engineered mice, overexpressing SRC-2 specifically in the prostate epithelium as a mouse model to examine the role of SRC-2 in prostate tumorigenesis. Over-expression of SRC-2 in PTEN heterozygous mice accelerates PTEN mutation induced tumor progression and develops a metastasis-prone cancer. We used microarrays to examine the molecular profile of prostate-specific SRC-2 overexpression adult dorsal-lateral prostate in comparison with that of control PTENF/+ heterozygous deletion mice.
2014-06-30 | GSE54678 | GEO
Project description:BRCA1 is biallelically deleted or mutated in at least 1.9% of prostate tumors, but whether BRCA1 deficiency influences resistance to androgen deprivation therapy (ADT) and prostate cancer development remains elusive. Here we surprisingly find that in human, BRCA1 heterozygous deletion is observed in approximately 13% of human prostate cancers, is more prevalent in neuroendocrine prostate tumors and predicts worse survival than BRCA1 homozygous deletion. In mice, we show that Brca1 heterozygosity (HET) but not Brca1 full inactivation (KO) accelerates early tumor development, invasion and resistance to ADT in Pten-null prostate tumors. Furthermore, pre-malignant tumors and organoids derived from Brca1 HET mice undergo neuroendocrine differentiation and exhibit elevated levels of the unfolded protein response potentially as a pro-survival mechanism, but not those of Brca1 KO. Our findings thus provide important insights into clinical management of prostate cancer patients, suggesting that patients heterozygous for Brca1 are prone to developing resistance to ADT and should be treated differently from patients with complete Brca1 loss.
2024-02-01 | GSE176280 | GEO
Project description:The PIP3/PI3K network is a central regulator of metabolism and is frequently activated in cancer, commonly by loss of the PIP3/PI(3,4)P2-phosphatase, PTEN. Despite huge investment, the drivers of the PI3K network in normal tissues and how they adapt to overactivation are unclear. We find that in healthy mouse prostate PI3K activity is driven by RTK/IRS signalling and constrained by pathway-feedback. In the absence of PTEN, the network is dramatically remodelled. A poorly understood, YXXM- and PIP3/PI(3,4)P2-binding PH domain-containing, adaptor, PLEKHS1, became the dominant activator and was required to sustain PIP3, AKT-phosphorylation and growth in PTEN-null prostate. This was because PLEKHS1 evaded pathway-feedback and experienced enhanced PI3K- and SRC-family kinase-dependent phosphorylation of Y258XXM, eliciting PI3K-activation. hPLEKHS1-mRNA and activating-Y419-phosphorylation of hSRC correlated with PI3K-pathway activity in human prostate cancers. We propose that in PTEN-null cells, receptor-independent, SRC-dependent tyrosine-phosphorylation of PLEKHS1 creates positive-feedback that escapes homeostasis, drives PIP3-signalling and supports tumour progression.
2023-08-23 | PXD043239 | Pride
Project description:PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/RbPE:-/- mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:-/- mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110β and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4, a known PC metastasis suppressor. In contrast, PTEN expression, which dampened these oncogenic behaviors, correlated with greater dependence on p110α plus AKT1. Our data suggest that metastatic PC aggressiveness is controlled by specific PI3K/AKT isoform combinations influenced by divergent Src activation or PTEN-loss pathways.
2023-11-01 | GSE242387 | GEO
Project description:Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent. Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival.
2016-12-14 | GSE92347 | GEO
Project description:Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent. Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival.
2016-12-20 | GSE92574 | GEO
Project description:The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.
2013-04-10 | MTBLS30 | MetaboLights
Project description:Experimental aim: identification of SRC-2 and SRC-3-related genes in MCF-7 breast cancer cells. Experimental workflow: 1. shRNA transduction. MCF-7 cells were transduced with a mix of lentiviral particles containing five individual lentiviral pLKO.1-puro short hairpin (sh) RNA plasmids targeting different sequences on SRC-2 or SRC-3 mRNA and a pLKO.1-puro empty vector control. The puromycin selections were maintained for three weeks to obtain cells containing stably integrated shRNA. 2. Sample preparation. RNA was extracted from eight independent replicates expressing the pLKO.1-puro empty shRNA vector (shKTR), from eight replicates of SRC-2 shRNA expressing cells (shSRC-2), and from seven replicates of SRC-3 shRNA expressing cells (shSRC-3). 300 ng of total RNA from each cell sample was biotin-labelled and amplified.
2019-07-01 | E-MTAB-7018 | biostudies-arrayexpress