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Journal of Cancer Research and Clinical Oncology

Published in:

01-12-2009 | Original Paper

Methylation analysis of SFRP genes family in cervical adenocarcinoma

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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2009

Abstract

Objectives

Aberrant activation of the Wnt/β-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/β-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/β-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.

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Title: Methylation analysis of SFRP genes family in cervical adenocarcinoma
Authors: Ya-Wen Lin
Ming-Tzeung Chung
Hung-Cheng Lai
Ming De Yan
Yu-Leung Shih
Cheng-Chang Chang
Mu-Hsien Yu
Publication date: 01-12-2009
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 12/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0613-5

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