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

Abstract

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.

• Authors: Stephen L Lessnick, Caroline S Dacwag, Todd R Golub
• Journal: Cancer cell (Cancer Cell) Vol. 1 Issue 4 Pg. 393-401 (May 2002) ISSN: 1535-6108 [Print] United States
• PMID: 12086853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• DNA Primers
• EWS-FLI fusion protein
• Oncogene Proteins, Fusion
• Proto-Oncogene Protein c-fli-1
• RNA-Binding Protein EWS
• Tetracyclines
• Transcription Factors
• Tumor Suppressor Protein p53

Topics

• Anti-Bacterial Agents (pharmacology)
• Bone Neoplasms (enzymology, genetics)
• Cell Division (physiology)
• Cell Survival (physiology)
• Cell Transformation, Neoplastic
• Cells, Cultured (cytology, metabolism)
• DNA Primers (chemistry)
• Fibroblasts (cytology)
• Gene Expression Profiling
• Humans
• Infant, Newborn
• Mutation
• Oligonucleotide Array Sequence Analysis
• Oncogene Proteins, Fusion (physiology)
• Proto-Oncogene Protein c-fli-1
• RNA-Binding Protein EWS
• Retroviridae (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoma, Ewing (enzymology, genetics)
• Tetracyclines
• Transcription Factors (physiology)
• Transfection
• Tumor Suppressor Protein p53 (genetics, metabolism)