論文 - 詳細
| RRC ID | 1369 |
|---|---|
| 著者 | Akahira J, Sugihashi Y, Suzuki T, Ito K, Niikura H, Moriya T, Nitta M, Okamura H, Inoue S, Sasano H, Okamura K, Yaegashi N. |
| タイトル | Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:In this study, we examined the promoter methylation status and expression of 14-3-3 sigma and evaluated its clinical significance in epithelial ovarian cancer. EXPERIMENTAL DESIGN:Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3 sigma gene and protein. RESULTS:Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P < 0.001). Treatment of 5-aza-2'-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3 sigma protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3 sigma protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3 sigma was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of >2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3 sigma immunoreactivity was significantly associated with overall survival (P = 0.0058). CONCLUSIONS:Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer. |
| 巻・号 | 10(8) |
| ページ | 2687-93 |
| 公開日 | 2004-4-15 |
| DOI | 10.1158/1078-0432.ccr-03-0510 |
| PMID | 15102672 |
| MeSH | 14-3-3 Proteins Adult Aged Biomarkers, Tumor / biosynthesis* Cell Line, Tumor CpG Islands DNA Methylation* DNA, Complementary / metabolism Disease Progression Epithelial Cells / metabolism* Exonucleases / biosynthesis* Exoribonucleases Female Gene Library Humans Immunohistochemistry Middle Aged Neoplasm Proteins / biosynthesis* Ovarian Neoplasms / metabolism* Ovarian Neoplasms / pathology Polymerase Chain Reaction Promoter Regions, Genetic Reverse Transcriptase Polymerase Chain Reaction Time Factors |
| IF | 10.107 |
| 引用数 | 86 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | OMC-3(RCB0755) JHOC-5(RCB1520) JHOS-3(RCB1546) HTOA(RCB0692) JHOS-2(RCB1521) |