Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor-specific translocations are common in tumors of mesenchymal origin. Whether the translocation determines the phenotype, or vice versa, is debatable. Ewing's family tumors (EFT) are consistently associated with an EWS-FLI1 translocation and a primitive neural phenotype. Histogenesis and classification are therefore uncertain. To test whether EWS-FLI1 fusion gene expression is responsible for the primitive neuroectodermal phenotype of EFT, we established a tetracycline-inducible EWS-FLI1 expression system in a rhabdomyosarcoma cell line RD. Cell morphology changed after EWS-FLI1 expression, resembling cultured EFT cells. Xenografts showed typical EFT features, distinct from tumors formed by parental RD. Neuron-specific microtubule gene MAPT, parasympathetic marker cholecystokinin, and epithelial marker keratin 18 were up-regulated. Conversely, myogenesis was diminished. Comparison of the up-regulated genes in RD-EF with the Ewing's signature genes identified important EWS-FLI1 downstream genes, many involved in neural crest differentiation. These results were validated by real-time reverse transcription-PCR analysis and RNA interference technology using small interfering RNA against EWS-FLI1 breakpoint. The present study shows that the neural phenotype of Ewing's tumors is attributable to the EWS-FLI1 expression and the resultant phenotype resembles developing neural crest. Such tumors have a limited neural phenotype regardless of tissue of origin. These findings challenge traditional views of histogenesis and tumor origin.
 ...
PMID:EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors. 1593 Feb 81

Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) has a characteristic chimeric oncogene EWS-FLI1, which results from chromosomal translocation t (11; 22), that is believed to initiate tumorigenesis of EWS/PNET. However, the specific details of EWS/PNET oncogenesis and exact role of EWS-FLI1 remain largely unknown. In this study we explored the role of EWS-FLI1 in tumor differentiation using an embryonal carcinoma cell line P19 as a model, with forced expression of EWS-FLI1 in these cells. EWS-FLI1 has been reported to promote neural differentiation in fibroblasts, mesenchymal stem cells and rhabdomyosarcoma cells. We show forced expression of EWS-FLI1 causes absence of retinoic acid-induced neural morphology, and decreases expression of neural-specific proteins MAPT and NCAM. Critical transcriptional factors for neural differentiation and stem cells are also altered in the presence of EWS-FLI1, including decreases in levels of Oct-3 and Pax-6, and an increase in the level of Id2, which is a target of EWS-FLI1. Increased proliferation and decreased apoptotic rates are also observed in P19 cells with forced expression of EWS-FLI1. Our results raise the possibility that arrest of neural differentiation by forced expression of EWS-FLI1 as observed in this study may result from dysregulation of the cell cycle and cell proliferation. Taken together, our results demonstrate that the modulation of neural differentiation in P19 cells which have a stem cell-like pluripotency in vitro can provide a novel model system to study the neural differentiation effects of EWS-FLI1 tumorigenesis of EWS/PNET.
 ...
PMID:Neural differentiation arrest in embryonal carcinoma cells with forced expression of EWS-FLI1. 1862 80