title: Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells.
abstract: The Ewing family of tumors are poorly differentiated pediatric solid tumors arising in bone and soft tissues from an unknown cell of origin. Ewing tumors are molecularly defined by in-frame genomic fusions that combine EWS with one of several ETS genes, most commonly FLI-1. We considered pluripotent marrow-derived stromal cells a likely candidate for the origin of Ewing tumors and assessed the effects of EWS/ETS proteins in this cell background. EWS/ETS expression in marrow-derived stromal cells caused a dramatic change in cellular morphology that was dependent on the presence of the ETS domain and unique to the fusion proteins. EWS/ETS fusion proteins blocked differentiation along osteogenic and adipogenic lineages, consistent with the undifferentiated appearance of Ewing tumors. Inhibition of differentiation may be an important function of EWS/ETS proteins in the genesis of Ewing tumors.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Enrique C
authors.initials: EC
authors.lastname: Torchia
authors.forename: Sobha
authors.initials: S
authors.lastname: Jaishankar
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Baker
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012512:Sarcoma, Ewing / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C072312:ERG protein, human; C497426:Fli1 protein, mouse; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG