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Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines

Cancer Gene Therapy volume 14, pages 927–933 (2007)Cite this article

Abstract

The extremely poor prognosis of patients with metastatic osteosarcoma indicates the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the biological activity of EDA-A2 against osteosarcoma-derived cell lines. We report that XEDAR is expressed in cell lines derived from osteosarcoma and adenoviral-mediated expression of EDA-A2 in these cells results in the induction of apoptosis via caspase activation and cell-cycle arrest in the G0/G1 phase. Treatment with EDA-A2 also upregulates the expression of alkaline phosphatase, a marker of osteogenic differentiation, in a caspase-dependent fashion. Collectively, our results suggest that EDA-A2 may be a promising agent for the gene therapy of osteosarcoma.

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Acknowledgements

This work was supported by Grant R01 DE 15189 from the National Institute of Dental and Craniofacial Research.

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Author notes

  1. B Chang and V Punj: These authors have contributed equally to this work.

Authors and Affiliations

  1. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA

    B Chang, M Shindo & P M Chaudhary

  2. Division of Hematology–Oncology, Department of Medicine, The Hillman Cancer Center, University of Pittsburgh, PA, USA

    V Punj & P M Chaudhary

  3. Department of Dermatology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan

    M Shindo

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  1. B Chang
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  2. V Punj
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  3. M Shindo
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  4. P M Chaudhary
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Corresponding author

Correspondence to P M Chaudhary.

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Chang, B., Punj, V., Shindo, M. et al. Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines. Cancer Gene Ther 14, 927–933 (2007). https://doi.org/10.1038/sj.cgt.7701078

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  • DOI: https://doi.org/10.1038/sj.cgt.7701078

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