EWS/Fli-1 Fusion Protein Is Involved in Neural Phenotype in Ewing^|^apos;s Sarcoma Cells

Abstract

Ewing's sarcoma (ES) and other peripheral primitive neuroectodermal tumor (PNET) show limited neural differentiation and are thought to have a neural crest origin. The fusion gene, EWS/Fli-1 found in ES and PNET are formed by a tumor specific 11; 22 chromosomal translocations. They have been shown to encode a transcriptional activator and promote cellular transformation. However, the precise biological functions of the fusion gene products remain to be elucidated. Especially it is controversial whether the gene products may inhibit neural differentiation or they may keep neural phenotype in ES. In the present study, we first investigated EWS/Fli-1 expression after induction of neural differentiation by addition of nerve growth factor (NGF) or c-AMP and demonstrated that EWS/Fli-1 protein expression did not change in response to those treatments. Moreover, overexpression of EWS/Fli-1 did not affect differentiation process of C6 glial cells. On the contrary, morphological differentiation and expression of NSE (neuron specific enolase) and trkA, one of the high-affinity NGF receptors, were inhibited in ES cells, in which the endogeneous EWS/Fli-1 protein was not detected. In conclusion, our data are compatible with a view that EWS/Fli-1 fusion gene may not inhibit neural differentiation process, but may play an important role in preserving the potentiality of neural phenotype in ES cells.