Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells

Oncogene. 1999 Sep 30;18(40):5506-13. doi: 10.1038/sj.onc.1202928.


Ewing's sarcomas express chimeric transcription factors resulting from a fusion of the amino terminus of the EWS gene to the carboxyl terminus of one of five ETS proteins. While the majority of tumors express EWS/FLI1 fusions, some Ewing's tumors contain variant chimeras such as EWS/ETV1 that have divergent ETS DNA-binding domains. In spite of their structural differences, both EWS/ETS fusions up regulate EAT-2, a previously described EWS/FLI1 target gene. In contrast to EWS/FLI1, NIH3T3 cells expressing EWS/ETV1 cannot form colonies in soft agar though coexpression of a dominant negative truncated ETV1 construct attenuates EWS/FLI1 mediated anchorage independent growth. When EWS/ETV1 or EWS/FLI1 expressing NIH3T3 cells are injected into SCID mice, tumors form more often and faster than with NIH-3T3 cells with empty vector controls. The tumorigenic potency of each EWS/ETS fusion is linked to its C-terminal structure, with the FLI1 C-terminus confering a greater tumorigenic potential than the corresponding ETV1 domain. The resulting EWS/ETV1 and EWS/FLI1 tumors closely resemble each other at both a macroscopic and a microscopic level. These tumors differ greatly from tumors formed by NIH3T3 cells expressing activated RAS. These data indicate that in spite of their structural differences, EWS/ETV1 and EWS/FLI1 promote oncogenesis via similar biologic pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / pathology
  • 3T3 Cells / transplantation
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone Neoplasms / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, ras
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / physiology*
  • Phenotype
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • Sarcoma, Ewing / genetics*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • Adaptor Proteins, Signal Transducing
  • EWS-ETV1 fusion protein, human
  • EWS-FLI fusion protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • SH2D1B protein, human
  • Sh2d1b1 protein, mouse
  • Transcription Factors