DNA methylation inhibits p53-mediated survivin repression

Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.


The molecular progression of endometrial cancer is poorly understood, and both genetic and epigenetic factors play a role. Survivin is a member of the inhibitor of apoptosis (IAP) gene family and contains a canonical CpG island that has been described as epigenetically regulated. As survivin is overexpressed in endometrial tumors, we hypothesized that hypomethylation could explain this expression pattern. Surprisingly, methylation-specific PCR and pyrosequencing showed that survivin was hypermethylated in endometrial tumors and correlated with increased survivin expression. We speculated that methylation could inhibit the binding of p53, a repressor of survivin expression. Our data indicates that demethylation of the survivin promoter by decitabine results in p53-dependent survivin repression and that p53 binding can be inhibited by DNA methylation. We are the first to report survivin de-repression by DNA methylation. We also present microarray data, which suggest that de-repression by methylation is a general mechanism of p53 regulation. Demethylation induced by decitabine is traditionally thought to be active in tumors by allowing the re-expression of tumor suppressor genes. However, our results indicate that an additional important mechanism is to decrease the expression of oncogenes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • DNA Methylation* / drug effects
  • Decitabine
  • Endometrial Neoplasms / metabolism*
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Tumor Suppressor Protein p53 / metabolism*


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Survivin
  • Tumor Suppressor Protein p53
  • Decitabine
  • Azacitidine