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Cancer Cell DOI:

The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts

Publication TypeJournal Article
Year of Publication2002
AuthorsLessnick, SL, Dacwag, CS, Golub, TR
JournalCancer Cell
Pages393 - 401
Date Published2002/05//
ISBN Number1535-6108
KeywordsAnti-Bacterial Agents, Bone Neoplasms, Cancer, Cell Division, Cell Survival, Cell Transformation, Cells, Cultured, DNA Primers, Fibroblasts, Gene Expression Profiling, Humans, Infant, Mutation, Neoplastic, Newborn, Oligonucleotide Array Sequence Analysis, Oncogen

Ewing's sarcoma is associated with a fusion between the EWS and FLI1 genes, forming an EWS/FLI fusion protein. We developed a system for the identification of cooperative mutations in this tumor through expression of EWS/FLI in primary human fibroblasts. Gene expression profiling demonstrated that this system recapitulates many features of Ewing's sarcoma. EWS/FLI-expressing cells underwent growth arrest, suggesting that growth arrest-abrogating collaborative mutations may be required for tumorigenesis. Expression profiling identified transcriptional upregulation of p53, and the growth arrest was rescued by inhibition of p53. These data support a role for p53 as a tumor suppressor in Ewing's sarcoma and demonstrate the use of transcriptional profiling of model systems in the identification of cooperating mutations in human cancer.