期刊
ONCOGENE
卷 20, 期 5, 页码 626-633出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204133
关键词
Ewing's sarcoma; Ewing family tumors; PDGF-C; EWS/FLI
资金
- NCI NIH HHS [R01 CA090666] Funding Source: Medline
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 Sa;coma 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.
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