EWS/FLI function varies in different cellular backgrounds.
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.
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-1150, USA.
Jeffrey P
JP
Zwerner
Jennifer
J
Guimbellot
William A
WA
May
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008222:Lymphokines; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation
C106031:EWS-FLI fusion protein; D008222:Lymphokines; D015514:Oncogene Proteins, Fusion; D010982:Platelet-Derived Growth Factor; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; C411423:platelet-derived growth factor C