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


CONCLUSIONS
Our study suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKK-1 silencing.
Lee
Jaehyouk
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Yoon
Young Soo
YS
Chung
Jae Hoon
JH
D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D006655:Histone Deacetylases