Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA177574 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Co-expression of genes with ERG in prostate cancers
| PRJNA177575 | ENA
Project description:ERG overexpression is the most frequent molecular alteration in prostate cancer. We analyzed different stages of prostate cancer to identify genes that were coexpressed with ERG overexpression. In primary prostate tumors, it was shown that TDRD1 expression was the strongest correlated gene with ERG overexpression and we suggest TDRD1 as a direct ERG target gene. 6 Prostate cancer cell lines and 11 prostate cancer xenografts are included in this study. Each sample was analyzed once.
2013-02-11 | E-GEOD-41407 | biostudies-arrayexpress
Project description:Expression data of EZH2-dependent genes in prostate cancer cell lines
| PRJNA170907 | ENA
Project description:Prostate cancer cell lines that express ERG acquire a neuron-like phenotype. The human prostate tumor cell line LNCap was transfected with lenti-ERG or control lenti-vector. Gene expression profiling was performed to establish the ERG-associated phenotype.
2014-03-18 | E-GEOD-55944 | biostudies-arrayexpress
Project description:Gene expression variations in prostate cancer cell lines
| PRJNA104593 | ENA
Project description:The TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer but its role in disease progression is still debated. In this study, we uncovered a novel molecular mechanism promoting progression in ERG-fusion positive prostate cancer. We show that ERG is methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within the internal auto-inhibitory domain. Mechanistically, K362 mono- methylation prevents intra-domain interactions, favors DNA binding and promotes ERG transcriptional and oncogenic activity in cellular and mouse models. Consistently with the involvement in ERG oncogenesis, we found that K362 methylation was associated with disease progression in ERG transgenic mouse models and was enhanced by PTEN deficiency and AKT activation, which promoted EZH2 substrate switching from histone H3K27 to ERG. Conversely, EZH2 inhibition blocked ERG methylation along with ERG-induced transcriptional and phenotypic reprogramming in cell cultures and ERG/PTEN mice. We found that ERG and EZH2 co-occupy several genomic regions forming prevalently co-activating complexes. The network of ERG/EZH2 co-regulated target genes was enriched of functionally aggressive features and was associated preferentially with concomitant ERG gain and PTEN loss, castration-resistance and adverse clinical outcome in prostate cancer patients. Collectively, these findings identify ERG methylation as a novel post-translational modification sustaining disease progression in ERG-positive prostate cancers. Our data also provide an attractive rationale for developing molecularly targeted therapeutics to antagonize ERG oncogenic activity.
2021-04-16 | GSE159471 | GEO
Project description:Deregulation of the Androgen Receptor (AR) transcriptional network is a common hallmark in prostate cancers. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of cofactors. In prostate cancers, AR transcription collaborators are frequently aberrantly over-expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, the prostate cancer recurrent fusion gene, ERG, was shown to promote tumor progression by acting as a repressor of AR signaling. However, the exact mechanics and the functional consequences associated with this crosstalk between ERG and AR still remains relatively unknown. Interestingly, through chromatin immunoprecipitation coupled with massively parallel sequencing, we discover that ERG and other commonly over-expressed transcriptional co-repressors (HDAC1, HDAC2, HDAC3 and EZH2) are wired into an AR-centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. We show that ERG represses several AR target genes involved in epithelial differentiation. Furthermore, we demonstrated that suppression of the androgen-induced gene, Vinculin, by ERG and histone deacetylases increases cancer cell invasiveness. From our results, we propose that ERG, histone deactelyases and the histone methyltransferase, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, in part through modulating the transcriptional output of AR. Gene expression profiling of human prostate cancer VCaP cells with time-course dihydrotestosterone (DHT) stimulation using microarrays. Triplicates were generated for each treatment/time point.
2012-04-26 | E-GEOD-28948 | biostudies-arrayexpress
Project description:Deregulation of the Androgen Receptor (AR) transcriptional network is a common hallmark in prostate cancers. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of cofactors. In prostate cancers, AR transcription collaborators are frequently aberrantly over-expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, the prostate cancer recurrent fusion gene, ERG, was shown to promote tumor progression by acting as a repressor of AR signaling. However, the exact mechanics and the functional consequences associated with this crosstalk between ERG and AR still remains relatively unknown. Interestingly, through chromatin immunoprecipitation coupled with massively parallel sequencing, we discover that ERG and other commonly over-expressed transcriptional co-repressors (HDAC1, HDAC2, HDAC3 and EZH2) are wired into an AR centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. We show that ERG represses several AR target genes involved in epithelial differentiation. Furthermore, we demonstrated that suppression of the androgen induced gene, Vinculin, by ERG and histone deacetylases increases cancer cell invasiveness. From our results, we propose that ERG, histone deactelyases and the histone methyltransferase, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, in part through modulating the transcriptional output of AR. Gene expression profiling of human prostate cancer VCaP cells with time course DHT stimulation using microarray.
2012-04-26 | E-GEOD-35540 | biostudies-arrayexpress
Project description:Bernasocchi T, El Tekle G, Bolis M, Svinkina T, Zoma M, Rinaldi A, Ceserani V, Janouskova H, Schram P, Carbone G, Alimonti A, Moch H, Carr SA, Udeshi ND, Theurillat JP. 2018.
While the co-operation of cancer driver genes in tumorigenesis has been studied, little is known about the interplay of driver mutations that never co-occur within the same cancer cells. The latter scenario has been identified in prostate cancer where recurrent gene fusions involving the oncogenic ERG transcription factor and point mutations in the ubiquitin ligase adaptor SPOP are strictly mutually exclusive. Nevertheless, the underlying basis of this observation is poorly understood. Here, we show that ERG and mutant SPOP, even though oncogenic on their own, are together synthetic sick. At the molecular level, both driver genes inhibit each other in a reciprocal manner. In ERG-driven tumors, wild type SPOP is required to dampen androgen receptor (AR) signaling and sustain ERG activity in part through its ability to degrade the bromodomain histone reader ZMYND11. Consequently, loss-of-function mutations in SPOP unleash excessive AR signaling and reduce ERG function. Conversely, oncogenic androgen receptor signaling driven by mutant SPOP is repressed by ERG. The incompatibility of mutant SPOP and ERG may help to understand why SPOP mutant tumors frequently harbor gene deletions in the chromatin-modifying enzyme CHD1. We find that mutant SPOP promotes the generation of ERG rearrangements in a CHD1-dependent manner. Thus, CHD1 gene deletions may protect SPOP-mutant tumors from ERG-mediated growth inhibition. Taken together, our findings reveal the existence of divergent and incompatible paths towards prostate cancer that converge on SPOP function.
| MSV000082915 | MassIVE