Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts

M. Ouchida, T. Ohno, Y. Fujimura, V. N. Rao, E. S.P. Reddy

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139 Citations (Scopus)

Abstract

Cytogenetic analysis of Ewing's sarcoma, primitive neuroectodermal tumors and Askin tumors revealed characteristic translocations t(11;22) or t(21;22). Molecular analysis of these translocations revealed 5'-region of EWS gene (from band 22q12) is fused to the 3'-region of either Fli-1 gene (from band 11q24) or erg gene (from band 21q22). Functional characterization of the EWS-Fli-1 and EWS-erg chimeric proteins suggested that they function as transcriptional activators. In order to develop therapeutic agents, it is essential to know whether expression of the EWS-fusion gene products is coupled to tumorigenicity of Ewing's sarcoma cells and if targeting the EWS-fusion products results in loss of tumorigenicity of Ewing's sarcoma cells. For this reason, we have made stable Ewing's sarcomas expressing antisense EWS-FLi-1 or EWS-erg transcripts by transfecting the antisense EWS-FLi-1 or EWS-erg expression plasmids. Expression of antisense EWS fusion transcripts resulted in a significant loss of endogenous EWS-Fli-1 and EWS-erg proteins in Ewing's sarcoma cells. These cells expressing antisense EWS fusion transcripts showed loss of anchorage independent growth and tumorigenicity in nude mice unlike the parental Ewing's sarcoma cells. These results demonstrate the necessity of a certain threshold level of expression of EWS-fusion products in the clonogenicity and tumorigenicity of Ewing's sarcoma cells and therefore emphasizes the importance of targeting the EWS-fusion products as a therapy for Ewing family of tumors.

Original languageEnglish
Pages (from-to)1049-1054
Number of pages6
JournalOncogene
Volume11
Issue number6
Publication statusPublished - 1995

Keywords

  • EWS
  • Ets
  • Ewing's sarcoma
  • RNA binding
  • Therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ouchida, M., Ohno, T., Fujimura, Y., Rao, V. N., & Reddy, E. S. P. (1995). Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene, 11(6), 1049-1054.