期刊
ONCOGENE
卷 28, 期 19, 页码 2046-2050出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.62
关键词
DNA methylation; endometrium; cancer
资金
- NIH [1P50CA098258-01]
- Rosalie B Hite Graduate Student Fellowship
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. Oncogene (2009) 28, 2046-2050; doi:10.1038/onc.2009.62; published online 13 April 2009
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