Decreased Expression of 14-3-3σ Is Associated with Advanced Disease in Human Epithelial Ovarian Cancer: Its Correlation with Aberrant DNA Methylation

Jun Ichi Akahira, Youko Sugihashi, Takashi Suzuki, Kiyoshi Ito, Hitoshi Niikura, Takuya Moriya, Makoto Nitta, Hitoshi Okamura, Satoshi Inoue, Hironobu Sasano, Kunihiro Okamura, Nobuo Yaegashi

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

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 < 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 >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.

Original languageEnglish
Pages (from-to)2687-2693
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number8
DOIs
Publication statusPublished - 2004 Apr 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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