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PRDM5 Identified as a Target of Epigenetic Silencing in Colorectal and Gastric Cancer

2007; American Association for Cancer Research; Volume: 13; Issue: 16 Linguagem: Inglês

10.1158/1078-0432.ccr-07-0305

1557-3265

Yoshiyuki Watanabe, Minoru Toyota, Yutaka Kondo, Hiromu Suzuki, Takashi Imai, Mutsumi Ohe-Toyota, Reo Maruyama, Masanori Nojima, Yasushi Sasaki, Yoshitaka Sekido, Hiroyoshi Hiratsuka, Yasuhisa Shinomura, Kohzoh Imai, Fumio Itoh, Takashi Tokino,

Genetic factors in colorectal cancer

Abstract 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 Lys27 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 Lys27 of histone H3) likely plays a key role in the progression of gastrointestinal cancers and may be a useful molecular marker.