PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis
Copyright policy )PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis
Ewing's Sarcoma family tumors (ESFT) are characterized by a translocation t(11:22) forming an aberrant transcription factor EWS-FLI1. Protein tyrosine phosphatase L1 (PTPL1) was identified as a gene upregulated by EWS-FLI1 in transfected cells by microarray. Our results show that PTPL1 is a transcriptional target of EWS-FLI1 both by chromatin immunoprecipitation and promoter activation studies. We demonstrate that PTPL1 is highly expressed in ESFT cells and patient tumors compared with normal tissues, with a trend towards higher expression in metastatic versus primary tumors. Reduction of PTPL1 protein in ESFT cells correlated with a significant reduction in both monolayer and soft-agar cell growth. In addition, these PTPL1-reduced cells were more sensitive to etoposide-induced apoptosis than the controls. We therefore report a novel transcriptional activation of a phosphatase involved in the oncogenesis of ESFT. Increasing interest in specific phosphatase inhibitors would allow PTPL1 to be evaluated as a therapeutic target in ESFT.
- University of Washington Medical Center United States
- Georgetown University Medical Center United States
Chromatin Immunoprecipitation, Oncogene Proteins, Fusion, Transcription, Genetic, Proto-Oncogene Protein c-fli-1, Protein Tyrosine Phosphatase, Non-Receptor Type 13, Bone Neoplasms, Sarcoma, Ewing, Mice, Phenotype, Cell Line, Tumor, Mutagenesis, Site-Directed, Animals, Humans, Cloning, Molecular, Protein Tyrosine Phosphatases, RNA-Binding Protein EWS, Protein Binding, Transcription Factors
Chromatin Immunoprecipitation, Oncogene Proteins, Fusion, Transcription, Genetic, Proto-Oncogene Protein c-fli-1, Protein Tyrosine Phosphatase, Non-Receptor Type 13, Bone Neoplasms, Sarcoma, Ewing, Mice, Phenotype, Cell Line, Tumor, Mutagenesis, Site-Directed, Animals, Humans, Cloning, Molecular, Protein Tyrosine Phosphatases, RNA-Binding Protein EWS, Protein Binding, Transcription Factors
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