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

Objective. Our study was designed to demonstrate that DICKKOPF-1 (DKX-1), encoding a secreted Writ 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 DKX-1. The chromatin immunoprecipitation assay was performed to determine whether HeLa cells recruit histone deacetylation for DKX-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 historic deacetylation in HeLa cells. Conclusion. Our study suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKX-1 silencing. (c) 2008 Elsevier Inc. All rights reserved.