TY - JOUR
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
N1 - Funding Information:
Acknowledgments We thank Dr. Hiromu Suzuki (First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan) for kindly providing the construct plasmid. This work was supported in part by National Science Council, Taiwan, Republic of China (ROC); grant numbers: the NSC96-2320-B-016-019-MY2, NSC96-3112-B-016-003, NSC97-3112-B-016-002; the Department of Health, Taiwan, Republic of China; grant number: DOH97-TD-I-111-TM005; Tri-Service General Hospital, Taiwan, ROC; grant numbers: TSGH-C97-7S01-S03; the Armed Forces Tao-Yuan General Hospital, Tao-Yuan, Taiwan, ROC; grant numbers: AFTYGH-9607, AFTYGH-9608.
PY - 2009/12
Y1 - 2009/12
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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U2 - 10.1007/s00432-009-0613-5
DO - 10.1007/s00432-009-0613-5
M3 - Article
C2 - 19513747
AN - SCOPUS:70349766097
SN - 0171-5216
VL - 135
SP - 1665
EP - 1674
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 12
ER -
