Methylation analysis of SFRP genes family in cervical adenocarcinoma.

Ya Wen Lin, Ming Tzeung Chung, Hung Cheng Lai, Ming De Yan, Yu Leung Shih, Cheng Chang Chang, Mu Hsien Yu

研究成果: 雜誌貢獻文章同行評審

44 引文 斯高帕斯(Scopus)

摘要

OBJECTIVES: Aberrant activation of the Wnt/beta-catenin signaling pathway is common in human cancers. Recently, we have shown that secreted frizzled-related proteins (SFRPs) are frequently methylated in cervical squamous cell carcinoma (SCC). Furthermore, reexpression of SFRP1 and SFRP2 could suppress tumor cell transformation and invasion. Here, we want to further investigate the methylation status and function of SFRPs in adenocarcinoma of uterine cervix. METHODS: The methylation status of SFRPs was assessed in 23 adenocarcinomas (AC), and 45 normal control swabs by methylation-specific polymerase chain reaction and bisulfite sequencing. Then, we used reexpression of SFRP5 in cervical cancer cell lines, HeLa3rd and CaSki, to study the role of SFRP5 in cervical adenocarcinoma by colony formation and invasion assays. Finally, we checked whether SFRP5 could repress the expression of Wnt/beta-catenin downstream genes by quantitative reverse transcription-polymerase chain reaction. RESULTS: The frequency of SFRP genes promoter hypermethylation in adenocarcinoma of cervix samples was 52.2% (12/23), 82.6% (19/23), 65.2% (15/23), and 73.9% (17/23), for SFRP1, SFRP2, SFRP4, and SFRP5, respectively. The frequency of SFRP1, SFRP2, SFRP4, and SFRP5 promoter methylation in adenocarcinoma was significantly higher than in normal control samples (P <0.001). Restoration of SFRP5 suppressed colony formation and invasive ability and inhibited expression of Wnt/beta-catenin downstream genes. CONCLUSIONS: Our data suggest that promoter hypermethylation of SFRPs is associated with cervical adenocarcinoma, which could be used for molecular screening of cervical adenocarcinoma in the future. Moreover, SFRP5 inhibits cervical tumorigenesis through interfering Wnt pathway in vitro.

原文英語
頁(從 - 到)1665-1674
頁數10
期刊Journal of Cancer Research and Clinical Oncology
135
發行號12
DOIs
出版狀態已發佈 - 十二月 2009
對外發佈Yes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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