Lee Jaehyouk, Yoon Young Soo, Chung Jae Hoon
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Gynecol Oncol. 2008 May;109(2):270-4. doi: 10.1016/j.ygyno.2008.01.034. Epub 2008 Apr 2.
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.
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.
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.
Our study suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKK-1 silencing.
我们的研究旨在证明，编码一种分泌型Wnt拮抗剂的Dickkopf-1（DKK-1）在宫颈癌细胞系中受到表观遗传改变的转录抑制。
对8种人宫颈癌细胞系进行甲基化特异性PCR，并对甲基化水平存在显著差异的4种细胞系进行亚硫酸氢盐测序，以确定DKK-1 5'端区域的CpG岛甲基化状态。进行染色质免疫沉淀试验，以确定HeLa细胞是否募集组蛋白去乙酰化来沉默DKK-1。
在所检测的8种宫颈癌细胞系中，有2种受独立的表观遗传失活机制调控；启动子CpG高甲基化是SNU-703细胞系中的主要表观遗传改变，而HeLa细胞系中则是组蛋白去乙酰化。
我们的研究表明，宫颈癌细胞系利用细胞系依赖性的、不同表观遗传机制来沉默DKK-1。
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