Transcriptional profiles LPC-HRas cells with or without ETV4 knockdown
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE184680 | GEO | 2021/10/30
REPOSITORIES: GEO
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Project description:Transcriptional profiles LPC-HRas cells with or without ETV4 knockdown
| PRJNA765637 | ENA
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: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:Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice. A backcross was generated using male Mus spretus and female FVB/N Hras-/- mice; female F1 hybrids were mated with male FVB/N Hras -/- or Hras -/+ mice to generate a backcross population. This series contains mice that were Hras -/-. Mice were aged to 8 weeks and a tail skin sample was snap frozen.
2015-03-01 | E-GEOD-60769 | biostudies-arrayexpress
Project description:Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice.
2015-03-01 | GSE60769 | GEO
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:ETS-related transcription factors ETV4 and ETV5 play crucial roles for organogenesis and morphogenesis. We compared the transcriptional profiles between wild-type and ETV4 and ETV5 double knockout (ETV4/5 dKO) ES cells by an oligo DNA microarray analysis. Self-renewal capacity and pluripotency are known to be controlled by an ES cell-specific transcription factor network; therefore, we focused on transcription-associated genes. Of 1258 transcription-related genes, 47 genes were significantly downregulated and 98 genes were significantly upregulated in ETV4/5 dKO ES cells. Several genes whose expression is specific to undifferentiated ES were repressed in ETV4/5 dKO ES cells. In contrast, expression of differentiation markers was enhanced in ETV4/5 dKO ES cells.
2015-09-13 | GSE47225 | GEO
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-08 | PXD012506 | Pride
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-12 | E-MTAB-7672 | biostudies-arrayexpress
Project description:All extant amniotes employ a single-layered epithelium of epiblasts as a starting material for gastrulation, suggesting the necessity of the epithelial structure for three germ layer derivation. Using a human embryonic stem cell (hESC) epithelium as a model system, we found that local epithelial crowding derepresses the neuroectoderm fate by spatiotemporal inactivation of ETV4. ETV4 serves as a genetic toggle switch that links cell density to lineage fates. Mechanistically, cell crowding blocks FGF receptor endocytosis by reduced cell-extracellular matrix (ECM) interaction. Disrupted endocytosis decreases ETV4 protein stability by ERK inactivation. Mathematical modeling of epithelial crowding demonstrates that the cooperativity of integrin-ECM interaction transforms the gradient of crowdedness into bistable ETV4 transition, which ensures the switch-like function of ETV4 in lineage determination. Our results propose local cell crowding in a stem cell epithelium as a key cellular mechanism for spatiotemporal regulation of lineage fates.
2024-03-12 | GSE183702 | GEO