Epigenetic alteration of secreted wnt antagonists in cervical cancer = 자궁경부암에서 분비형 Wnt 길항유전자들의 후유전적 이상

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Epigenetic gene silencing of secreted antagonists in the Wnt/\beta-catenin signaling pathway was known to play an important role in many human cancers. My 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. Two out of eight cervical cancer cell lines examined were found to be regulated by either of the two epigenetic mechanisms. Promoter CpG hypermethylation constitutes a major epigenetic alteration in SNU-703, and histone deacetylation in HeLa cells. These findings were consistent with the restoration of DKK-1 transcription after treatment with DNA-demethylating agent or histone deacetylase (HDAC) inhibitor in the relevant cell lines. Conventional methods for DNA methylation analysis e.g., MSP, COBRA, and bisulfite sequencing were used to examine CpG-island methylation status at the 5’-end region of DKK-1. In order to perform accurate estimation of DNA methylation level, nine cervical cancer cell lines were subjected to capillary electrophoresis. These data suggests that cervical cancer cell lines exploit cell line-dependent, differential epigenetic mechanisms for DKK-1 silencing. To obtain methylation profile of the secreted Wnt-antagonist gene family in cervical cancer cell lines, qualitative and quantitative assays for promoter methylation of DKK-3, SFRP1, SFRP2, SFRP4, SFRP5 and WIF-1 were carried out by MSP and CE. The result suggests that hypermethylation at the 5’-end region of the secreted Wnt-antagonist gene family is a common event in cervical cancer cell lines. Aberrant promoter methylation profile of these genes can be used as a diagnostic biomarker and a molecular target for future anti-cancer therapeutics.
Advisors
Chung, Jae-Hoonresearcher정재훈researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2008
Identifier
295330/325007  / 000975290
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2008.2, [ vi, 81 p. ]

Keywords

Cervical cancer; Secreted Wnt antagonist; DNA methylation; histone deacetylation; 자궁경부암; 분비형 Wnt 길항유전자; DNA 메틸화; Histone 디아세틸화; Cervical cancer; Secreted Wnt antagonist; DNA methylation; histone deacetylation; 자궁경부암; 분비형 Wnt 길항유전자; DNA 메틸화; Histone 디아세틸화

URI
http://hdl.handle.net/10203/27636
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=295330&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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