Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: Correlation with epigenetic inactivation by aberrant DNA methylation
Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: Correlation with epigenetic inactivation by aberrant DNA methylation
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DOI：
10.1111/j.1440-1827.2007.02169.x
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发表时间：
2007-11
影响因子：
2.2
通讯作者：
J. Akahira;Fumihiko Suzuki;Takashi Suzuki;I. Miura;Noriko Kamogawa;Y. Miki;K. Ito;N. Yaegashi;H. Sasano
中科院分区：
文献类型：
--
作者：
J. Akahira;Fumihiko Suzuki;Takashi Suzuki;I. Miura;Noriko Kamogawa;Y. Miki;K. Ito;N. Yaegashi;H. Sasano
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。本研究的目的是检测RIZ 1在卵巢癌中的表达，并探讨其临床病理意义。对RIZ 1进行免疫组织化学和定量逆转录聚合酶链反应（RT-PCR），并检查其临床病理学意义。并对RIZ 1基因的甲基化状态进行了研究。6例正常乳腺组织、5例良性乳腺组织和4例交界性乳腺组织中RIZ 1蛋白均呈阳性表达。卵巢癌组织中RIZ 1阳性率为32.9%（54/164）。RIZ 1表达降低与组织学类型（P < 0.0001）、肿瘤分级（P = 0.0153）、临床分期（P = 0.0345）和Ki 67指数（P = 0.0117）相关，但与患者的总体预后无关（P = 0.519）。在2/9个细胞系和5/69个卵巢癌组织中检测到甲基化条带。甲基化的细胞系中RIZ 1相对表达的中位数显著低于未甲基化的细胞系（P = 0.0404），5-氮杂-2 ′脱氧胞苷处理导致RIZ 1的去甲基化和重新表达。RIZ 1的低表达可能在上皮性卵巢癌的发生和/或发展中起重要作用，并且被认为部分由异常的DNA甲基化引起。
The retinoblastoma protein‐interacting zinc finger gene (RIZ1) is considered a tumor suppressor gene. The purpose of the present study was to examine the expression of RIZ1 and evaluate its clinicopathological significance in ovarian carcinoma. Immunohistochemistry and quantitative reverse transcription–polymerase chain reaction (RT‐PCR) was performed for RIZ1 and its clinicopathological significance was examined. DNA methylation status of RIZ1 was also studied. All (6/6) of the normal, 5/9 of benign, and 4/9 of borderline tissues were positive for RIZ1 protein. In ovarian cancer tissues 32.9% (54/164) were positive for RIZ1. Decreased expression of RIZ1 was significantly correlated with histological subtypes (P < 0.0001), high tumor grade (P = 0.0153) and advanced clinical stage (P = 0.0345), and high Ki67 index (P = 0.0117) but was not associated with the overall prognoses of the patients (P = 0.519). The presence of methylated band was detected in 2/9 cell lines, and 5/69 ovarian cancer tissues. Median values of relative RIZ1 expression in cell lines with methylation were significantly lower than those without methylation (P = 0.0404), and treatment of 5‐aza‐2′deoxycitidine resulted in demethylation and re‐expression of RIZ1. Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of epithelial ovarian carcinoma, and is considered to be caused in part by aberrant DNA methylation.