In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 8 ( 2004-04-15), p. 2687-2693
Abstract:
Purpose: In this study, we examined the promoter methylation status and expression of 14-3-3σ 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 14-3-3σ 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 14-3-3σ gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P & lt; 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 14-3-3σ protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3σ protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3σ was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of & gt;2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3σ immunoreactivity was significantly associated with overall survival (P = 0.0058). Conclusions: Our findings suggest that 14-3-3σ is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-03-0510
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2004
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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