Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA126299 | ENA |
REPOSITORIES: ENA
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Project description:Chromosomal abnormalities that give rise to elevated expression levels of the ETS genes ETV1, ETV4, ETV5, or ERG are prevalent in prostate cancer, but the function of these transcription factors in carcinogenesis is not clear. Previous work implicates ERG, ETV1, and ETV5 as regulators of invasive growth but not transformation in cell lines. Here we show that the PC3 prostate cancer cell line provides a model system to study the over-expression of ETV4. Anchorage independent growth assays and microarray analysis indicate that high ETV4 expression is critical for the transformation phenotype of PC3 cells. However, genes up-regulated upon ETV4 over-expression were very similar to genes up-regulated by ETV1 over-expression in the RWPE-1 normal prostate cell line. Together these data indicate that the ETV4 dependent transformation phenotype observed in PC3 cells is due to the genetic background of the cell line, rather than a distinct characteristic of ETV4. Furthermore, these findings suggest that the function of ETS genes in prostate cancer may differ based on other genetic alterations in a tumor. Two sets of two color experiments. First is PC3 cells expressing one of two independent ETV4 shRNAs versus PC3 cells expressing a control shRNA (luciferase). Second is RWPE-1 cells expressing 3xFlag tagged ETV4 versus RWPE-1 cells with a control (empty) vector.
2011-03-24 | E-GEOD-21209 | biostudies-arrayexpress
Project description:Chromosomal abnormalities that give rise to elevated expression levels of the ETS genes ETV1, ETV4, ETV5, or ERG are prevalent in prostate cancer, but the function of these transcription factors in carcinogenesis is not clear. Previous work implicates ERG, ETV1, and ETV5 as regulators of invasive growth but not transformation in cell lines. Here we show that the PC3 prostate cancer cell line provides a model system to study the over-expression of ETV4. Anchorage independent growth assays and microarray analysis indicate that high ETV4 expression is critical for the transformation phenotype of PC3 cells. However, genes up-regulated upon ETV4 over-expression were very similar to genes up-regulated by ETV1 over-expression in the RWPE-1 normal prostate cell line. Together these data indicate that the ETV4 dependent transformation phenotype observed in PC3 cells is due to the genetic background of the cell line, rather than a distinct characteristic of ETV4. Furthermore, these findings suggest that the function of ETS genes in prostate cancer may differ based on other genetic alterations in a tumor.
2011-03-25 | GSE21209 | GEO
Project description:Chromosomal translocations or upregulations involving ETS transcription factor are frequent events in prostate cancer pathogenesis and significantly co-occurrence with p53 or PTEN loss. Caused by the low stabilities of ETS proteins in cytosol, mouse models with aberrant expression of wild type ETS transcription factors had subtle phenotypes and only drive prostate cancer progression in the setting of Pten loss. Here we show that prostate specific aberrant expression of mutated ETV4 (V70P71D72-AAA, ETV4-AAA), which is resistence to COP1 mediated protein degradation, results in more stabilized ETV4 protein in mouse prostate. We found that ETV4-AAA mice develop marked prostatic intraepithelial neoplasia (mPin) and p53-dependent cell senescence within 2 weeks, but without tumor development when aged. Interestingly, ETV4-AAA positive cells reduce dramatically in a PTEN loss background, which means that there is no cooperation between ETV4-AAA and PTEN loss. Aberrant ETV4-AAA expression promotes progression of mPin to prostatic adenocarcinoma in a Tp53 deficiency or haploinsufficiency background. In contrast to PTEN loss induced mouse prostate cancers which loss NKX3.1 expression and resistant to castration therapy, these ETV4-AAA tumor cells well maintain AR and NKX3.1 expression and are sensitive to castration therapy.
2021-01-01 | GSE130311 | GEO
Project description:ETS transcription factors have recently emerged as important elements in the pathogenesis of prostate cancer (PCa). ETS gene rearrangements leading to over-expression of ETS factors, like ERG, ETV1 and ETV4, are found in about 50% of prostate tumors. While the oncogenic potential of translocated ETS has been demonstrated in several contexts, the impact of endogenously expressed ETS factors on prostate tumorigenesis has been largely overlooked. Here we show that the epithelial-specific ETS factor ESE3, which is normally expressed in basal prostate epithelial (PrE) cells and frequently down-regulated in prostate tumors, serves as gatekeeper to maintain cell differentiation and its down-regulation leads to the acquisition of mesenchymal, stem cell (SC) and tumorigenic properties. ESE3 exerts this function by regulating critical genes involved in the epithelial to mesenchymal transition (EMT) and cell “stemness” and maintaining the equilibrium between cell differentiation and proliferation. Loss of ESE3 may be an important step in prostate tumorigenesis. Keywords: prostate epithelial cells, prostate cancer, gene expression profiling, ETS genes, EMT, cancer stem cells
2012-06-05 | GSE23197 | GEO
Project description:Chromosomal rearrangements resulting in the fusion of TMRPSS2, an androgen-regulated gene, and the ETS family transcription factor ERG occur in over half of prostate cancers. However, the mechanism by which ERG promotes oncogenic gene expression and proliferation remains incompletely understood. Here, we identify a binding interaction between ERG and the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complex, which is conserved among other ETS factors, including ETV1, ETV4, and ETV5. We find that ERG drives genome-wide retargeting of BAF complexes in a manner dependent on binding of ERG to the ETS DNA motif. Moreover, ERG requires intact BAF complexes for chromatin occupancy and BAF complex ATPase activity for target gene regulation. In a prostate organoid model, BAF complexes are required for ERG-mediated basal-to-luminal transition, a hallmark of ERG activity in prostate cancer. These observations suggest a fundamental interdependence between ETS transcription factors and BAF chromatin remodeling complexes in cancer.
2018-08-02 | GSE110656 | GEO
Project description:Chromosomal rearrangements resulting in the fusion of TMRPSS2, an androgen-regulated gene, and the ETS family transcription factor ERG occur in over half of prostate cancers. However, the mechanism by which ERG promotes oncogenic gene expression and proliferation remains incompletely understood. Here, we identify a binding interaction between ERG and the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complex, which is conserved among other ETS factors, including ETV1, ETV4, and ETV5. We find that ERG drives genome-wide retargeting of BAF complexes in a manner dependent on binding of ERG to the ETS DNA motif. Moreover, ERG requires intact BAF complexes for chromatin occupancy and BAF complex ATPase activity for target gene regulation. In a prostate organoid model, BAF complexes are required for ERG-mediated basal-to-luminal transition, a hallmark of ERG activity in prostate cancer. These observations suggest a fundamental interdependence between ETS transcription factors and BAF chromatin remodeling complexes in cancer.
2018-08-02 | GSE110655 | GEO
Project description:Our in vitro binding studies support a model whereby MED25 exhibits multivalent interactions with a subset of related ETS factors, ETV1/4/5. We hypothesize that the interaction would allow for coregulation of genes by ETV1/4/5 and MED25, acting perhaps to link the ETVs to the Mediator complex. To explore this possibility, we compared the genome occupancy for FLAG-tagged MED25 and ETV4 in the prostate cancer cell line PC3, which overexpresses ETV4. We also tested for relevance of MED25 and ETV4 binding to for gene expression in PC3s. We found a high degree of overlap in the FLAG-MED25 and ETV4 ChIPs datasets consistent with our model, and also identified a subset of target genes co-dependent on Med25 and ETV4.
2019-06-28 | GSE133447 | GEO
Project description:Our in vitro binding studies support a model whereby MED25 exhibits multivalent interactions with a subset of related ETS factors, ETV1/4/5. We hypothesize that the interaction would allow for coregulation of genes by ETV1/4/5 and MED25, acting perhaps to link the ETVs to the Mediator complex. To explore this possibility, we compared the genome occupancy for FLAG-tagged MED25 and ETV4 in the prostate cancer cell line PC3, which overexpresses ETV4. We also tested for relevance of MED25 and ETV4 binding to for gene expression in PC3s. We found a high degree of overlap in the FLAG-MED25 and ETV4 ChIPs datasets consistent with our model, and also identified a subset of target genes co-dependent on Med25 and ETV4.
2019-06-28 | GSE133445 | GEO
Project description:The protein Glycine-N-Acyltransferase Like 1 (GLYATL1) is involved in detoxification of benzoate and other xenobiotics and is expressed in liver and kidney. Through In silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry we show that GLYATL1 is overexpressed in primary prostate cancer compared to metastatic prostate cancer and benign prostatic tissue. Low grade cancers had higher GLYATL1 expression compared to high grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways. In summary, our study characterizes the expression GLYATL1 in prostate cancer and explore its regulation mechanism. Future studies are needed to decipher the biological significance of these findings.
2019-12-17 | GSE130395 | GEO
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. 16 samples were analyzed, comprised of four replicates each of four different biological conditions. RNA from U0126 treated RWPE-1 empty vector cell RNA serves as a control for each experiment. Cell lines have retroviral expression constructs expressing either empty vector, Flag-ERG, or Flag-ETV1.
2011-10-18 | E-GEOD-29438 | biostudies-arrayexpress