Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA141513 | ENA |
REPOSITORIES: ENA
Similar Datasets
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. ChIP sequencing two transcription factors in PC3 cells, four transcription factors plus a FLAG control in RWPE-1 cells and input DNA sequencing from each cell line.
2011-10-19 | E-GEOD-29808 | biostudies-arrayexpress
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
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.
2011-10-19 | GSE29438 | 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.
2011-10-20 | GSE29808 | GEO
Project description:Oncogenic ETS proteins replace activated Ras/MAPK signaling in prostate cells.
| PRJNA140921 | ENA
Project description:Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner.
2017-02-13 | GSE86239 | GEO
Project description:Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner.
2017-02-13 | GSE86238 | GEO
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the 'Ras-addiction' of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells. The si-Ctrl, si-Med23 and si-Elk1 A549 cells were cultured in the normal condition. Then the cells were harvested for RNA extraction and hybridization on Affymetrix microarrays. The analysis contain 9 samples. si-Ctrl cells have three replicates (si-Ctrl#1, si-Ctrl#2 and si-Ctrl#3), and the si-Med23 or si-Elk1 group contains three different cell lines that harbor three different RNAi oligos against Med23 or Elk1 (si-Med23A, B, C and si-Elk1A, B, C).
2013-08-31 | E-GEOD-40517 | biostudies-arrayexpress
Project description:Ephexin1 was initially identified as a neuronal guanine nucleotide exchange factor involved in the control of neuronal development and synaptic homeostasis. Here, we demonstrate that the induction of Ephexin1 expression by an oncogenic K-Ras mutation amplifies the MAPK signaling via direct interaction with oncogenic Ras and contributes to colon and lung tumorigenesis. Ephexin1 cooperates with mutant Ras to accelerate skin tumorigenesis in vivo. In addition, we have demonstrated that the functionally relevant interaction between oncogenic K-Ras and Ephexin1. Together, these findings suggest that Ephexin1 serves as a positive regulator of Ras-driven oncogenesis and potentially represents a novel target for therapeutic intervention.
2021-10-27 | GSE147809 | GEO
Project description:Mitochondrial dysfunction causes biophysical, metabolic and signalling changes that alter homeostasis and reprogram cells. We used a Drosophila model in which TFAM is overexpressed in the nervous system with or without Ras/MAPK pathway inhibition, by knock-down of the ETS transcription factor pointed, to investigate the how mitochondrial dysfunction and Ras/MAPK signalling affect the transcriptome. We used microarray analysis to investigate gene expression in cases of mitochondrial dysfunction in the CNS with or without Ras/MAPK pathway inhibition by knock-down of pointed (Pnt) and anterior open (Aop).
2018-05-05 | GSE114054 | GEO