Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2003-07, Vol.63 (13), p.3464-3468
Main Authors: TORCHIA, Enrique C, JAISHANKAR, Sobha, BAKER, Suzanne J
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Animals
Biological and medical sciences
Bone Marrow Cells - cytology
Cell Differentiation - physiology
Cyclin-Dependent Kinase Inhibitor p16 - deficiency
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyclin-Dependent Kinase Inhibitor p16 - physiology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Medical sciences
Medulloblastoma - genetics
Medulloblastoma - pathology
Mice
Mice, Knockout
Oncogene Proteins - genetics
Oncogene Proteins - physiology
Oncogene Proteins, Fusion - genetics
Oncogene Proteins, Fusion - physiology
Pluripotent Stem Cells - cytology
Polymerase Chain Reaction
Proto-Oncogene Protein c-fli-1
Proto-Oncogene Proteins
RNA-Binding Protein EWS - deficiency
RNA-Binding Protein EWS - genetics
RNA-Binding Protein EWS - physiology
Sarcoma, Ewing - genetics
Trans-Activators - genetics
Trans-Activators - physiology
Transcription Factors - genetics
Transcription Factors - physiology
Transcriptional Regulator ERG
Tumor Cells, Cultured
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Summary: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.
ISSN:0008-5472
1538-7445