Identification of the a kinase anchor protein 12 (AKAP12) gene as a candidate tumor suppressor of hepatocellular carcinoma
Identification of the a kinase anchor protein 12 (AKAP12) gene as a candidate tumor suppressor of hepatocellular carcinoma
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DOI：
10.1002/jso.22135
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发表时间：
2012-03-01
影响因子：
2.5
通讯作者：
Kodera, Y.
中科院分区：
文献类型：
--
作者：
Hayashi, M.;Nomoto, S.;Kodera, Y.
背景资料：肝细胞癌（Hepatocellular carcinoma，HCC）是一个严重的健康问题，寻找新的肿瘤相关基因是一项迫切的任务。方法：为了有效地检测肿瘤相关基因，我们对单个手术HCC标本进行了双组合阵列分析，包括表达阵列和单核苷酸多态性（single nucleotide polymorphism，SNP）阵列。表达阵列分析确定AKAP 12是HCC组织中与非癌相邻肝组织相比表达降低的基因之一。此外，48例HCC组织中AKAP 12的表达水平显著低于正常组织（P < 0.001），且表达下调与总生存率显著相关（P = 0.003）。SNP芯片分析显示AKAP 12所在的6 q24-q25位点未出现染色体缺失。相反，在48个HCC样本中的41个中观察到AKAP 12启动子区域的超甲基化。然后，我们证实，AKAP 12基因的重新表达发生后5-氮杂-2 '-脱氧胞苷（5-aza-dC）治疗通过直接序列分析的AKAP 12启动子区域在HCC细胞line.Conclusions：目前的数据表明，AKAP 12是下调癌组织中通过启动子甲基化，并可能有一个作用，作为一个候选的肝癌抑癌基因。外科肿瘤学杂志2012; 105：381-386. (C)2011 Wiley Periodicals，Inc.
Background: Hepatocellular carcinoma (HCC) is a major health problem, and identification of new tumor-related genes is an urgent task.Methods: To detect tumor-related genes effectively, we performed double-combination array analysis, which consisted of an expression array and a single nucleotide polymorphism (SNP) array of a single surgical HCC specimen.Results: Expression array analysis identified AKAP12 as one of the genes with reduced expression in HCC tissues when compared with non-cancerous adjacent hepatic tissues. In addition, AKAP12 expression levels in tumor tissues from 48 HCC samples were significantly lower (P < 0.001) than those in normal tissues, and the downregulation was significantly correlated with poor overall survival rate (P = 0.003). However, SNP array analysis revealed that locus 6q24-q25 where AKAP12 was located did not show chromosomal deletion. In contrast, hypermethylation in the AKAP12 promoter regions was observed in 41 of 48 HCC samples. We then confirmed that AKAP12 gene re-expression occurs after 5-aza-2'-deoxycytidine (5-aza-dC) treatment through direct sequence analysis of the AKAP12 promoter region in HCC cell lines.Conclusions: The current data suggest that AKAP12 is downregulated in cancer tissues through promoter hypermethylation, and may have a role as a candidate tumor suppressor gene for HCC. J. Surg. Oncol. 2012; 105: 381-386. (C) 2011 Wiley Periodicals, Inc.