PRDM5 identified as a target of epigenetic silencing in colorectal and gastric cancer

被引:82
作者
Watanabe, Yoshiyuki
Toyota, Minoru
Kondo, Yutaka
Suzuki, Hiromu
Imai, Takashi
Ohe-Toyota, Mutsumi
Maruyama, Reo
Nojima, Masanori
Sasaki, Yasushi
Sekido, Yoshitaka
Hiratsuka, Hiroyoshi
Shinomura, Yasuhisa
Imai, Kohzoh
Itoh, Fumio
Tokino, Takashi
机构
[1] Sapporo Med Univ, Dept Internal Med 1, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
[2] Sapporo Med Univ, Dept Mol Biol, Canc Res Inst, Sapporo, Hokkaido, Japan
[3] Sapporo Med Univ, Dept Publ Hlth, Sapporo, Hokkaido, Japan
[4] Sapporo Med Univ, Dept Oral Surg, Sapporo, Hokkaido, Japan
[5] St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan
[6] JST, PRESTO, Kawaguchi, Japan
[7] Aichi Canc Ctr, Div Mol Oncol, Nagoya, Aichi 464, Japan
关键词
D O I
10.1158/1078-0432.CCR-07-0305
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that play key roles during cell differentiation and malignant transformation. The aim of the present study was to begin to examine the involvement of epigenetic alteration of PRDM expression in gastric and colorectal cancer. Experimental Design: We used real-time PCR to assess expression of PRDM1-17. In addition, we used bisulfite PCR to assess DNA methylation and chromatin immunoprecipitation to assess histone modification in colorectal and gastric cancer cell lines lacking PRDM5 expression. Results: Among the 17 PRDM family genes tested, we found that PRDM5 is the most frequently silenced in colorectal and gastric cancer cell lines. Silencing of PRDM5 was mediated by either DNA methylation or trimethylation of Lys(27) of histone H3. Introduction of PRDM5 into cancer cells suppressed cell growth, suggesting that it acts as a tumor suppressor in gastrointestinal cancers. Methylation of PRDM5 was detected in 6.6% (4 of 61) of primary colorectal and 50.0% (39 of 78) of primary gastric cancers but not in noncancerous tissue samples collected from areas adjacent to the tumors. Conclusions: Our data suggest that epigenetic alteration of PRDM5 (e.g., methylation of its 5'-CpG island or trimethylation of Lys(27) of histone H3) likely plays a key role in the progression of gastrointestinal cancers and may be a useful molecular marker.
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页码:4786 / 4794
页数:9
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