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PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis

Oncogene volume 24, pages 2715–2722 (2005)Cite this article

Abstract

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.

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Abbreviations

ESFT:

Ewing's Sarcoma family tumors

IGF-IR:

insulin-like growth factor-I receptor

IRS-1:

insulin receptor substrate 1

PTPL1:

protein tyrosine phosphatase L1

PTP:

protein tyrosine phosphatase

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Acknowledgements

We appreciate the technical help of Hatice Özel Abaan, Kelsey McCarty, and Kamal Pathak, the assistance of Bob Fenton in the preparation of viral reagents, Marc Ladanyi for providing us unstained sections of the tissue multiarrays, and the valuable suggestions of Anton Wellstein. This work generously supported by the Children's Cancer Foundation (JT) and R01 CA88004 (JT).

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  1. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA

    Ogan D Abaan, Amy Levenson, Osman Khan, Priscilla A Furth, Aykut Üren & Jeffrey A Toretsky

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  1. Ogan D Abaan
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  2. Amy Levenson
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Correspondence to Jeffrey A Toretsky.

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Abaan, O., Levenson, A., Khan, O. et al. PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis. Oncogene 24, 2715–2722 (2005). https://doi.org/10.1038/sj.onc.1208247

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