Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines
- PMID: 18377964
- DOI: 10.1016/j.ygyno.2008.01.034
Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines
Abstract
Objective: Our study was designed to demonstrate that DICKKOPF-1 (DKK-1), encoding a secreted Wnt antagonist, is transcriptionally repressed by epigenetic alterations in cervical carcinoma cell lines.
Methods: Methylation-specific PCR for 8 human cervical cancer cell lines and bisulfite sequencing for 4 cell lines exhibiting significant difference in methylation levels were used to determine CpG-island methylation status at the 5'-end region of DKK-1. The chromatin immunoprecipitation assay was performed to determine whether HeLa cells recruit histone deacetylation for DKK-1 silencing.
Results: Two out of eight cervical cancer cell lines examined were found to be regulated by independent epigenetic inactivation mechanisms; promoter CpG hypermethylation constitutes a major epigenetic alteration in SNU-703, and histone deacetylation in HeLa cells.
Conclusion: Our study suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKK-1 silencing.
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