• Open Access

Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers

Authors

  • Toshio Takada,

    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
    2. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Yukiko Yagi,

    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
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  • Takao Maekita,

    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
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  • Masayoshi Imura,

    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
    2. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Shunsuke Nakagawa,

    1. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Sai-Wah Tsao,

    1. Department of Anatomy, Faculty of Medicine, University of Hong Kong, SAR, Hong Kong, China
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  • Kazuaki Miyamoto,

    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
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  • Osamu Yoshino,

    1. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Toshiharu Yasugi,

    1. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Yuji Taketani,

    1. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655
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  • Toshikazu Ushijima

    Corresponding author
    1. Carcinogenesis Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
      To whom correspondence should be addressed. E-mail: tushijim@ncc.go.jp
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To whom correspondence should be addressed. E-mail: tushijim@ncc.go.jp

Abstract

The SFRP1 gene on chromosome 8p11.2 encodes a Wnt signaling antagonist, and was recently demonstrated to be a new tumor suppressor that is inactivated by promoter methylation in human colon cancers. Here, we analyzed promoter methylation of the SFRP1 gene in human ovarian cancers, in which loss of heterozygosity in 8p is frequently observed and involvement of the Wnt signaling pathway has been suggested. Methylation-specific PCR (MSP) analysis showed that four of 13 ovarian cancer cell lines and two of 17 primary ovarian cancers had methylated SFRP1, while an immortalized ovarian epithelial cell line, HOSE, and seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell lines with the methylation, SFRP1 was not expressed at all as determined by quantitative RT-PCR analysis. A cell line with SFRP1 methylation, MCAS, was treated with a demethylating agent, 5-aza-2′-deoxycytidine, and demethylation of the promoter and re-expression of SFRP1 were observed. These results show that SFRP1 is inactivated by promoter methylation in human ovarian cancers, as well as colon cancers.

Abbreviations:
SFRP1

secreted frizzled-related protein 1

Ancillary