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- Title
PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors.
- Authors
Zwerner, Jeffrey P; May, William A
- Abstract
The aberrant transcription factors associated with many human malignancies function by deregulation of tumorigenic pathways. However, identification of these pathways has come slowly. Virtually all cases of Ewing's Sarcoma and peripheral Primitive Neuroectodermal Tumor (PNET) are associated with aberrant transcription factors which fuse amino-terminal EWS with the DNA binding moiety of an ETS transcription factor (FLI-1 in 90% of cases). Attempts to identify the downstream targets of these chimeras in the Ewing Family Tumors (EFT) on the basis of differential gene regulation have produced little association with tumor biology. As an alternative approach, we have used highly efficient retroviral systems to biologically screen cDNA derived from cells transformed by EWS/FLI-1. We have identified the recently described PDGF-C as target of EWS/ETS transcriptional deregulation. This transcriptional deregulation is specific to EWS/FLI. PDGF-C possesses substantial biologic activity in vitro and in vivo. It is expressed in EFT cell lines and in primary tumors. Within these EFT cell lines, PDGF-C expression is dependent upon EWS/FLI activity. These results suggest that PDGF-C may be a significant mediator of EWS/FLI driven oncogenesis. Oncogene (2001) 20, 626–633.
- Subjects
GROWTH factors; EWING'S sarcoma; TUMORS; TRANSCRIPTION factors
- Publication
Oncogene, 2001, Vol 20, Issue 5, p626
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204133