Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA113125 | ENA |
REPOSITORIES: ENA
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Project description:OBJECTIVE: Previous expression microarray analyses have failed to take into consideration the genetic heterogeneity and complex patterns of ERG gene alteration frequently found in cancerous prostates. The objective of this study is for the first time, to integrate the mapping of ERG gene alterations with the collection of expression microarray data. PATIENTS AND METHODS: We have deterimined genome-wide expression levels with Affymetrix GeneChip Human Exon 1.0 ST arrays using RNA prepared from 35 specimens of prostate cancer from 28 prostates. RESULTS: The expression profiles exhibit clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG gene status. Through analysis of the data we identify a subgoup of cancers lacking ERG gene rearrangements that exhibit an outlier pattern of SPINK1 mRNA expression. We also show that a major distinction between ERG gene rearranged and non-rearranged cancers involves the levels of expression of genes linked to exposure to beta-estradiol, and to retinoic acid. CONCLUSIONS: Our studies show that expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG gene status are the major determinants of poor clinical outcome. Keywords: disease state analysis
2009-08-01 | GSE12378 | GEO
Project description:Microarray expression profiling has currently failed to provide a consistent classification for human prostate cancer. Such classifications are important because they provide a framework for the identification of new biomarkers of clinical behavior and for the development of targeted therapies. We hypothesize that previous studies have been unsuccessful because of their failure to take into account the well documented occurrence of prostate cancer multifocality and genetic heterogeneity. We have invented a novel method for collecting whole RNALater preserved ‘research slices’ from prostatectomy specimens that, for the first time, allows the mapping of multifocality and of genetic heterogeneity in prostate cancer to be integrated with the selection of samples for expression microarray analysis. For each specimen we will construct a map of the regions of cancer and of their ERG gene rearrangement status from whole mount formalin fixed sections immediately juxtaposed to the ‘research slice’. Only foci of cancers containing a homogeneous pattern of ERG gene alteration will be selected for study. A pilot study has already demonstrated the feasibility of this approach, and provides initial evidence that cancers may be stratified into at least two prognostically distinct categories. Novel biomarkers defining distinct prostate cancer categories will be verified and validated in future studies linked to clinical trials.
2017-03-13 | GSE94767 | 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:Translocations of ETS transcription factors are driver mutations in diverse cancers. We investigated the genomic network of the ETS fusion EWS/FLI1 in Ewing's sarcoma (ESFT) as a model of ETS-driven tumorigenesis. ChIP-Seq and transcriptional analysis identified E2F3 as a principle co-factor of EWSFLI1 defining functionally distinct gene sets. While EWS/FLI1 binding independent of E2F3 predominantly associated with repressed differentiation genes, significant co-localization with E2F3 was discovered at proximal promoters of activated growth-related genes. Thus, EWS/FLI1 promotes oncogenesis by simultaneously perturbing differentiation state and augmenting the expression of genes co-regulated by E2F3. Integration of additional E2F3 and ERG localization data from prostate cancer containing TMPRSS2/ERG verified that the ETS-E2F module is also found in prostate cancer and may be of general relevance to ETS driven cancers. Timecourse with 6 timepoints of a doxicyclin inducible EWS-FLI1 knockdown in the A673 Ewing's Sarcoma celline
2013-07-01 | E-GEOD-27524 | biostudies-arrayexpress
Project description:SND1 and its partner MTDH promote cancer and therapeutic resistance; however, the mechanisms responsible for their function and potential cooperation with other oncogenes are not completely understood. We report here that oncoprotein ERG binds to the SND1/MTDH protein complex via the Tudor domain of SND1. ERG is an ETS-domain transcriptional factor, which is recombined and overexpressed in approximately half of human prostate cancers. siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout of SND1 in human prostate epithelium cell lines revealed a critical role of SND1 in proliferation of ERG-overexpressing prostate epithelial cells. Transcriptional analysis of ERG-positive human prostate cancer cells demonstrated significant overlap between genes regulated by ERG and SND1. Mechanistically, we found that ERG promoted nuclear localization of SND1/MTDH. Significantly, forced nuclear localization of SND1 by addition of exogenous nuclear localization sequences (NLS) prominently increased its growth promoting function irrespective of the status of ERG expression. To determine if SND1 is necessary for prostate cancer tumorigenesis in vivo, we generated mice with prostate-epithelium-specific deletion of Snd1. We found that inactivation of Snd1 did not impact normal prostate gland homeostasis. However, prostate epithelium-specific deletion of Snd1 in autochthonous mouse model of prostate cancer (PB-Cre/ERG/PTENflox/flox mice) showed greatly reduced invasive cancer growth and tumor burden. Moreover, gene expression analysis revealed a significant overlap between in vivo prostate transcriptional signatures of ERG and Snd1. We conclude that SND1 plays a critical role in prostate tumorigenesis and targeting SND1 may represent a potential therapeutic target in prostate cancer.
2023-09-11 | GSE212840 | GEO
Project description:Chromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. How these factors contribute to tumorigenesis and whether they play similar in vivo roles remain elusive. We show that ERG and ETV1 control a common transcriptional network but in an opposing fashion. In mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus, either factors cooperated with Pten-loss, leading to localized cancer, but only ETV1 supported development of advanced adenocarcinoma, likely through enhancement of androgen receptor signaling and steroid biosynthesis. Indeed, ETV1 expression promotes autonomous testosterone production, which may contribute to tumor progression to castration-resistant prostate cancer. Patient data confirmed association of ETV1 expression with aggressive disease. We conclude that despite many shared targets, ERG and ETV1 contribute differently to prostate tumor biology. Hence, prostate cancers with these fusions should be considered as distinct subtypes for patient stratification and therapy. Genomic targets of ERG and ETV1 transcription factors were identified by antibody-mediated and biotin-mediated ChIP-chip in human VCaP and LNCaP cells, respectively.
2013-03-01 | E-GEOD-39357 | biostudies-arrayexpress
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: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 | GSE41408 | 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.
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