DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer
DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer
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DOI：
10.1111/j.1349-7006.2006.00338.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.7
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Hasegawa, Yasuhisa;Matsubara, Akio;Yasui, Wataru
视网膜母细胞瘤蛋白相互作用锌指基因RIZ 1被认为是一种肿瘤抑制基因。RIZ 1在几种人类癌症中因突变、缺失和DNA甲基化而失活。本研究探讨前列腺癌组织中RIZ 1基因甲基化与p53基因突变的关系。总共分析了47例淋巴结阴性PCa（I-III期）。甲基化特异性聚合酶链反应检测RIZ 1基因的DNA甲基化在20（42.6%）的47 PCa组织。RIZ 1基因的DNA甲基化与临床病理特征无关。RIZ 1的DNA甲基化倾向于在具有高Gleason评分的PCa标本中（16/30，53.3%）比在具有低Gleason评分的PCa标本中（4/17，23.5%）更频繁地存在;然而，这种趋势没有统计学显著性（P = 0.0675）。47例PCa标本中，4例（8.5%）经免疫组化染色观察到p53细胞核聚集。所有4例p53核积聚的PCa标本均为III期疾病，并显示RIZ 1的DNA甲基化。然而，在其余43例无p53核积聚的癌症中，仅在16例（37.2%）标本中观察到RIZ 1的DNA甲基化（P = 0.0272）。在这三种PCa细胞系中，只有PC 3细胞系由于DNA甲基化而显示出RIZ 1 mRNA的丢失，并且这种丢失通过用去甲基化剂5-氮杂-2 '-脱氧胞苷处理而得到纠正。这些结果表明，RIZ 1的转录失活异常DNA甲基化可能有助于前列腺癌的发生。遗传改变可能与PCa的表观遗传改变相关。
The retinoblastoma protein-interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node-negative PCa (stages I-III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation-specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa.