Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes

Kouji Banno, Megumi Yanokura, Makiko Kawaguchi, Yoshiko Kuwabara, Jyunko Akiyoshi, Yusuke Kobayashi, Takashi Iwata, Akira Hirasawa, Takuma Fujii, Nobuyuki Susumu, Kastumi Tsukazaki, Daisuke Aoki

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30 Citations (Scopus)

Abstract

A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalInternational Journal of Oncology
Volume31
Issue number4
Publication statusPublished - 01-10-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Banno, K., Yanokura, M., Kawaguchi, M., Kuwabara, Y., Akiyoshi, J., Kobayashi, Y., Iwata, T., Hirasawa, A., Fujii, T., Susumu, N., Tsukazaki, K., & Aoki, D. (2007). Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. International Journal of Oncology, 31(4), 713-720.