title: Promoter methylation of SFRPs gene family in cervical cancer.
abstract: OBJECTIVE
  Oncogenic activation of the Wnt/beta-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear.
  
  
  METHODS
  The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls.
  
  
  RESULTS
  The SFRP1 promoter was hypermethylated in 33.9% of SCC, 8.2% of HSIL, 2.2% of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7% of SCC, 16.3% of HSIL, 15.6% LSIL and 4.4% normal tissues. The SFRP4 promoter was hypermethylated in 67.9% of SCC, 36.7% of HSIL, 4.4% of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1% of SCC, 4.1% of HSIL, 13.3% of LSIL and 4.4% normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P<0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0% vs 15.2%, respectively, P<0.05).
  
  
  CONCLUSIONS
  Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ming-Tzeung
authors.initials: MT
authors.lastname: Chung
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Yan
authors.forename: Yu-Lueng
authors.initials: YL
authors.lastname: Shih
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Chang
authors.forename: Mu-Hsien
authors.initials: MH
authors.lastname: Yu
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Lin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109618:SFRP2 protein, human; C118723:SFRP4 protein, human; C118511:SFRP5 protein, human