Scientific Publications

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

Publication TypeJournal Article
AuthorsLessnick, Stephen L., Dacwag Caroline S., and Golub Todd R.
AbstractEwing'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.
Year of Publication2002
JournalCancer Cell
Pages393 - 401
Date Published (YYYY/MM/DD)2002/05//
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