Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker

Masashi Takawa, Ken Masuda, Masaki Kunizaki, Yataro Daigo, Katsunori Takagi, Yukiko Iwai, Hyun Soo Cho, Gouji Toyokawa, Yuka Yamane, Kazuhiro Maejima, Helen I. Field, Takaaki Kobayashi, Takayuki Akasu, Masanori Sugiyama, Eijyu Tsuchiya, Yutaka Atomi, Bruce A.J. Ponder, Yusuke Nakamura, Ryuji Hamamoto

研究成果: Contribution to journalArticle査読

147 被引用数 (Scopus)

抄録

The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P<0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P=0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment.

本文言語英語
ページ(範囲)1298-1305
ページ数8
ジャーナルCancer Science
102
7
DOI
出版ステータス出版済み - 7 2011

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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