EWS/FLI function varies in different cellular backgrounds.

Academic Article

Abstract

  • EWS/FLI and other EWS/ets chimeric transcription factors play a central role in the biology of the Ewing family tumors. As with many oncogenes, EWS/FLI biologic activity can be demonstrated in a limited range of cellular contexts. To investigate the causes of this restriction, we demonstrate that two immortalized fibroblast lines resistant to EWS/FLI transformation, Rat1 and Yal7, express stable levels of EWS/FLI protein. Despite their resistance to EWS/FLI, Rat1 and Yal7 can be transformed by the potent EWS/FLI downstream mediator PDGF-C. In contrast to NIH3T3, the EWS/FLI resistant lines show no upregulation of PDGF-C in response to EWS/FLI, demonstrating differential EWS/FLI function in different cellular backgrounds. This phenomenon of differential function can also be demonstrated for several other NIH3T3 targets of EWS/FLI. Despite the correlation between anchorage-independent growth and PDGF-C induction, PDGF-C does not fully reproduce all aspects of the EWS/FLI phenotype in NIH3T3 cells. These results further point to the importance of PDGF-C in mediating EWS/FLI in vitro transformation and suggest caution in assuming that a transcription factor will produce identical effects in different cellular backgrounds.
  • Published In

    Keywords

  • Animals, Blotting, Northern, Blotting, Western, Cell Transformation, Neoplastic, Fibroblasts, Gene Expression Regulation, Neoplastic, Humans, Lymphokines, Mice, Mice, SCID, Neoplasms, Experimental, Oncogene Proteins, Fusion, Phenotype, Platelet-Derived Growth Factor, Proto-Oncogene Protein c-fli-1, RNA-Binding Protein EWS, Sarcoma, Ewing, Transcription Factors, Up-Regulation
  • Author List

  • Zwerner JP; Guimbellot J; May WA
  • Start Page

  • 414
  • End Page

  • 419
  • Volume

  • 290
  • Issue

  • 2