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Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma
- フォーマット:
- 論文
- 責任表示:
- Yamaguchi, Junpei ; Sasaki, Motoko ; Sato, Yasunori ; Itatsu, Keita ; Harada, Kenichi ; Zen, Yoh ; Ikeda, Hiroko ; Nimura, Yuji ; Nagino, Masato ; Nakanuma, Yasuni
- 言語:
- 英語
- 出版情報:
- Japanese Cancer Association / Blackwell Publishing Ltd, 2010-02-01
- 著者名:
Yamaguchi, Junpei Sasaki, Motoko Sato, Yasunori Itatsu, Keita Harada, Kenichi Zen, Yoh Ikeda, Hiroko Nimura, Yuji Nagino, Masato Nakanuma, Yasuni - 掲載情報:
- Cancer Science
- ISSN:
- 1347-9032
- 巻:
- 101
- 通号:
- 2
- 開始ページ:
- 355
- 終了ページ:
- 362
- バージョン:
- publisher
- 概要:
- 医薬保健研究域医学系<br />Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subunit of polycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor s … uppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16INK4a, E-cadherin, and p21were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. © 2009 Japanese Cancer Association. 続きを見る
- URL:
- http://hdl.handle.net/2297/45959
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