Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines

ObjectiveOur 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.MethodsMethylation-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.ResultsTwo 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.ConclusionOur study suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKK-1 silencing.