Co-expression of genes with ERG in prostate cancers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41408 | GEO | 2013/02/11
SECONDARY ACCESSION(S): PRJNA177575
REPOSITORIES: GEO
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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. 48 Prostate cancer samples from radical prostatectomies were included in this study. These samples contained more than 70% cancer and less than 30% stromal tissue. Each sample was analyzed once.
2013-02-11 | E-GEOD-41408 | biostudies-arrayexpress
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.
2013-02-11 | GSE41407 | GEO
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:Chromosomal translocations juxtaposing the androgen-responsive TMPRSS2 promoter with the ETS-family transcription factor ERG result in aberrant ERG up-regulation in approximately 50% of prostate cancers. Studies to date have demonstrated important roles of ERG in inducing oncogenic properties of prostate cancer. Its molecular mechanisms of action, however, are yet to be fully understood. To address these questions, we generated engineered LNCaP cells with ERG overexpression followed by LEF1 knockdown as well as control cell lines. To further investigate the role of LEF1 in ERG fusion positive samples, we also knockdown ERG in VCaP cell line. We performed microarray analysis on LNCaP cells with ERG overexpression followed by LEF1 knockdown using siRNA. We also knockdown endogenous ERG in fusion-positive cell line VCaP.
2013-05-29 | E-GEOD-47423 | biostudies-arrayexpress
Project description:Recently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior. To further elucidate the mechanism by which T/ERG executes the EMT program at large, we took a genome-wide approach and conducted micro-array based comparison between EP-AR and EP-AR T/ERG cells
2010-12-30 | GSE22010 | GEO
Project description:ERG is a transcriptional factor, which is recombined with promoter of TMPRSS2 and prominently overexpressed in half of human prostate cancers. The mechanisms of ERG-mediated oncogenesis are not completely understood. We performed an unbiased Mass Spectrometry screen for ERG-binding proteins and found that ERG binds to MTDH/SND1 protein complex in prostate cancer cells. We determined that ERG binds to the SND1/MTDH protein complex via SND1 and this interaction plays a critical role in ERG-mediated cancer.
2023-03-22 | PXD036882 | Pride
Project description:Recently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior. To further elucidate the mechanism by which T/ERG executes the EMT program at large, we took a genome-wide approach and conducted micro-array based comparison between EP-AR and EP-AR T/ERG cells Four biological replicate EP-AR and EP-AR T/ERG cell lines were infected in two different infections, two of each were used for expression analysis.
2010-12-30 | E-GEOD-22010 | biostudies-arrayexpress
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:Structural rearrangements leading to the TMPRSS2:ERG (T2E) fusion typify ~50% of prostate tumors and result in overexpression of the ERG transcription factor. Using T2E and non-T2E primary prostate tumors, we assessed the impact of ERG overexpression on chromatin by integrating ChIP-seq against H3K27ac, a chromatin modification found at active cis-regulatory elements, with paired genomic and expression data. We show that T2E tumors have a consistent and distinct cis-regulatory landscape to non-T2E tumors which drives their unique transcriptional profile. The T2E-specific cis-regulatory landscape is driven by ERG-mediated co-option of prostate master transcription factors HOXB13 and FOXA1 and is typified by Cluster Of Regulatory Elements (COREs) including one spreading into the ERG locus of the structurally rearranged allele. This gives rise to a cis-regulatory element within the rearranged ERG gene that contributes to ERG overexpression. The unique cis-regulatory landscape in T2E primary prostate tumors also reveals the activation of the NOTCH signalling pathway. Accordingly, chemical NOTCH pathway inhibition limited the invasive nature of T2E prostate cancer cells, revealing an actionable vulnerability against T2E prostate tumors. Taken together, our work delineates the role of ERG over-expression in co-opting master transcription factors to deploy a unique cis-regulatory landscape inducing a dependency on NOTCH signaling in T2E prostate tumors.
2017-07-25 | GSE96652 | 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