ArticleThe Biochemical journal2007
The EWS-Oct-4 fusion gene encodes a transforming gene.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The self-renewal function of Oct-4 can be replaced by the EWS-Oct-4 fusion protein in embryonic stem cells.Cellular and molecular life sciences : CMLS · 2025Article
- Pluripotency Stemness and Cancer: More Questions than Answers.Advances in experimental medicine and biology · 2022Article
- Molecular mechanisms and pathobiology of oncogenic fusion transcripts in epithelial tumors.Oncotarget · 2019Review
- Self-renewal gene tracking to identify tumour-initiating cells associated with metastatic potential.Oncogene · 2012Article
- Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance.The American journal of pathology · 2010Article
- Oct-4 controls cell-cycle progression of embryonic stem cells.The Biochemical journal · 2010Article
- EWS-Oct-4B, an alternative EWS-Oct-4 fusion gene, is a potent oncogene linked to human epithelial tumours.British journal of cancer · 2010Article
- Evaluation of Spinal Fusion Using Bone Marrow Derived Mesenchymal Stem Cells with or without Fibroblast Growth Factor-4.Journal of Korean Neurosurgical Society · 2009Article
- Epidermal neural crest stem cells (EPI-NCSC) and pluripotency.Stem cell reviews · 2008Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The t(6;22)(p21;q12) translocation associated with human bone and soft-tissue tumours results in a chimaeric molecule fusing the NTD (N-terminal domain) of the EWS (Ewing's sarcoma) gene to the CTD (C-terminal domain) of the Oct-4 (octamer-4) embryonic gene. Since the N-terminal domains of EWS and Oct-4 are structurally different, in the present study we have assessed the functional consequences of the EWS-Oct-4 fusion. We find that this chimaeric gene encodes a nuclear protein which binds DNA with the same sequence specificity as the parental Oct-4 protein. Comparison of the transactivation properties of EWS-Oct-4 and Oct-4 indicates that the former has higher transactivation activity for a known target reporter gene containing Oct-4 binding. Deletion analysis of the functional domains of EWS-Oct-4 indicates that the EWS (NTD), the POU domain and the CTD of EWS-Oct-4 are necessary for full transactivation potential. EWS-Oct-4 induced the expression of fgf-4 (fibroblast growth factor 4) and nanog, which are potent mitogens as well as Oct-4 downstream target genes whose promoters contain potential Oct-4-binding sites. Finally, ectopic expression of EWS-Oct-4 in Oct-4-null ZHBTc4 ES (embryonic stem) cells resulted in increased tumorigenic growth potential in nude mice. These results suggest that the oncogenic effect of the t(6;22) translocation is due to the EWS-Oct-4 chimaeric protein and that fusion of the EWS NTD to the Oct-4 DNA-binding domain produces a transforming chimaeric product.
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Registered trials
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