Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation.

摘要: Ewings sarcoma and primitive neuroectodermal tumors (ES/PNET) are characterized by the fusion of N-terminus EWS gene to C-terminus a member ETS family transcription factors. While such proteins thought play dominant oncogenic roles, it is unlikely that single genetic alteration itself will support cellular transformation. Given EWS/FLI1 only able transform immortalized 3T3 fibroblasts 30% ES/PNET contain homozygous deletion p16 locus, likely other events required for oncogenesis. Here we describe complementary mechanism utilized in establishment tumors. has capacity induce apoptosis growth arrest normal MEFs. Such effects prevent stable expression protein these cells. When expressed p16, p19ARF, or p53 deficient MEFs, apoptotic attenuated, creating environment permissive protein. loss tumor suppressor sufficient establish EWS/FLI1, transformation requires further perturbation.