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Promoter methylation of SFRPs gene family in cervical cancer.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2009 Feb; Vol. 112 (2), pp. 301-6. Date of Electronic Publication: 2008 Nov 26. - Publication Year :
- 2009
-
Abstract
- Objectives: 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.<br />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.<br />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).<br />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.
- Subjects :
- Adaptor Proteins, Signal Transducing
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Case-Control Studies
Eye Proteins genetics
Female
Gene Silencing
HeLa Cells
Humans
Intercellular Signaling Peptides and Proteins genetics
Neoplasm Staging
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Uterine Cervical Neoplasms pathology
Uterine Cervical Dysplasia genetics
Uterine Cervical Dysplasia pathology
DNA Methylation
Membrane Proteins genetics
Proto-Oncogene Proteins genetics
Uterine Cervical Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 112
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 19038436
- Full Text :
- https://doi.org/10.1016/j.ygyno.2008.10.004