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PubMed · 14567998

EWS/FLI function varies in different cellular backgrounds.

Jeffrey P Zwerner·Jennifer Guimbellot·William A May
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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.

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AnimalsBlotting, NorthernBlotting, WesternCell Transformation, NeoplasticFibroblastsGene Expression Regulation, NeoplasticHumansLymphokinesMiceMice, SCIDNeoplasms, ExperimentalOncogene Proteins, FusionPhenotypePlatelet-Derived Growth FactorProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingTranscription FactorsUp-RegulationComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Jeffrey P Zwerner, Jennifer Guimbellot, William A May. 2003-11-01. EWS/FLI function varies in different cellular backgrounds.. https://doi.org/10.1016/s0014-4827(03)00371-9

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