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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1665-1674
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume135
Issue number12
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

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Methylation
Adenocarcinoma
Genes
Wnt Signaling Pathway
beta Catenin
Cervix Uteri
Polymerase Chain Reaction
FRZB protein
Uterine Cervical Neoplasms
Reverse Transcription
Squamous Cell Carcinoma
Neoplasms
Carcinogenesis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Methylation analysis of SFRP genes family in cervical adenocarcinoma. / Lin, Ya Wen; Chung, Ming Tzeung; Lai, Hung Cheng; De Yan, Ming; Shih, Yu Leung; Chang, Cheng Chang; Yu, Mu Hsien.

In: Journal of Cancer Research and Clinical Oncology, Vol. 135, No. 12, 12.2009, p. 1665-1674.

Research output: Contribution to journalArticle

Lin, Ya Wen ; Chung, Ming Tzeung ; Lai, Hung Cheng ; De Yan, Ming ; Shih, Yu Leung ; Chang, Cheng Chang ; Yu, Mu Hsien. / Methylation analysis of SFRP genes family in cervical adenocarcinoma. In: Journal of Cancer Research and Clinical Oncology. 2009 ; Vol. 135, No. 12. pp. 1665-1674.
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title = "Methylation analysis of SFRP genes family in cervical adenocarcinoma.",
abstract = "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.",
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T1 - Methylation analysis of SFRP genes family in cervical adenocarcinoma.

AU - Lin, Ya Wen

AU - Chung, Ming Tzeung

AU - Lai, Hung Cheng

AU - De Yan, Ming

AU - Shih, Yu Leung

AU - Chang, Cheng Chang

AU - Yu, Mu Hsien

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N2 - 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.

AB - 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.

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