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Article

Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma

  • Authors:
    • Sebastian Wolf
    • Beate Hagl
    • Roland Kappler
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, D-80337 Munich, Germany
  • Pages: 1727-1735
    |
    Published online on: February 27, 2014
       https://doi.org/10.3892/ijo.2014.2312
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Abstract

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of infancy and although therapy has improved over the years, mortality is still fairly high. The establishment of new treatments has been hampered by the limited knowledge of the molecular mechanisms driving development of RMS. One characteristic of cancer cells is aberrant DNA methylation, which could lead to silencing of tumor suppressor genes. However, only a few epigenetically silenced genes have been described in RMS so far. We performed an expression profiling analysis of three RMS cell lines that were treated with the demethylating agent 5'-aza-2'-deoxycytidine (5-Aza‑dC) facilitating re-expression of epigenetically silenced genes. This treatment induced the gene BMP2 (bone morphogenetic protein 2) throughout all cell lines. Detailed methylation analysis of CpG sites in the BMP2 promoter region by bisulfite sequencing and methylation-specific PCR revealed that a high degree of DNA methylation is causatively associated with the suppression of BMP2 in RMS cells. Consequently, treatment of the RMS cell lines with 5-Aza-dC resulted in DNA demethylation of the BMP2 promoter, most prominently in alveolar RMS. Supplementation of recombinant human BMP2 (rhBMP2) led to a reduced viability of RMS cells. Altogether, these findings suggest that suppression of BMP2 by epigenetic silencing may play a critical role in the genesis of RMS, thereby providing a rationale for the development of a new treatment strategy for RMS.
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Copy and paste a formatted citation
Spandidos Publications style
Wolf S, Hagl B and Kappler R: Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma. Int J Oncol 44: 1727-1735, 2014.
APA
Wolf, S., Hagl, B., & Kappler, R. (2014). Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma. International Journal of Oncology, 44, 1727-1735. https://doi.org/10.3892/ijo.2014.2312
MLA
Wolf, S., Hagl, B., Kappler, R."Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma". International Journal of Oncology 44.5 (2014): 1727-1735.
Chicago
Wolf, S., Hagl, B., Kappler, R."Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma". International Journal of Oncology 44, no. 5 (2014): 1727-1735. https://doi.org/10.3892/ijo.2014.2312
Copy and paste a formatted citation
x
Spandidos Publications style
Wolf S, Hagl B and Kappler R: Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma. Int J Oncol 44: 1727-1735, 2014.
APA
Wolf, S., Hagl, B., & Kappler, R. (2014). Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma. International Journal of Oncology, 44, 1727-1735. https://doi.org/10.3892/ijo.2014.2312
MLA
Wolf, S., Hagl, B., Kappler, R."Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma". International Journal of Oncology 44.5 (2014): 1727-1735.
Chicago
Wolf, S., Hagl, B., Kappler, R."Identification of BMP2 as an epigenetically silenced growth inhibitor in rhabdomyosarcoma". International Journal of Oncology 44, no. 5 (2014): 1727-1735. https://doi.org/10.3892/ijo.2014.2312
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