FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors

Shoko Kitade, Ichiro Onoyama, Hiroaki Kobayashi, Hiroshi Yagi, Sachiko Yoshida, Masaya Kato, Ryosuke Tsunematsu, Kazuo Asanoma, Kenzo Sonoda, Norio Wake, Kenichiro Hata, Keiichi I. Nakayama, Kiyoko Kato

研究成果: ジャーナルへの寄稿記事

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FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c-Myc, cyclin E, Notch and c-Jun. FBXW7 is a known tumor-suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors (P < 0.01). FBXW7 expression levels in serous carcinoma samples were the lowest among four major histological subtypes. In addition, p53-mutated ovarian cancer samples showed significantly lower levels of FBXW7 expression compared with p53 wild-type cancer samples (P < 0.001). DNA methylation arrays and bisulfite PCR sequencing experiments revealed that 5′-upstream regions of FBXW7 gene in p53-mutated samples were significantly higher methylated compared with those in p53 wild-type samples (P < 0.01). This data indicates that p53 mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7 5′-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was associated with p53 mutations and the DNA methylation status of the 5′-upstream regions of FBXW7.

元の言語英語
ページ(範囲)1399-1405
ページ数7
ジャーナルCancer Science
107
発行部数10
DOI
出版物ステータス出版済み - 10 1 2016

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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