1. Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines
- Author
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Jaehyouk Lee, Jae Hoon Chung, and Young Soo Yoon
- Subjects
Bisulfite sequencing ,Cell ,Uterine Cervical Neoplasms ,Histone Deacetylases ,Epigenesis, Genetic ,HeLa ,Cell Line, Tumor ,medicine ,Humans ,Gene Silencing ,Cancer epigenetics ,Epigenetics ,Promoter Regions, Genetic ,biology ,Obstetrics and Gynecology ,DNA Methylation ,biology.organism_classification ,Molecular biology ,Wnt Proteins ,Histone ,medicine.anatomical_structure ,Oncology ,DNA methylation ,biology.protein ,Cancer research ,Intercellular Signaling Peptides and Proteins ,CpG Islands ,Female ,Chromatin immunoprecipitation ,HeLa Cells - 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.
- Published
- 2008
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