Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas
Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas
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DOI：
10.1111/j.1365-2559.2011.03798.x
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发表时间：
2011-04-01
期刊：
影响因子：
6.4
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
--
作者：
Sekine, Shigeki;Ogawa, Reiko;Kanai, Yae
目的：α-甲基酰基辅酶A消旋酶（AMACR）在大多数肝细胞癌（HCC）中以不同水平表达，但AMACR过度表达的意义仍然难以捉摸。本研究的目的是探讨 HCC 中 AMACR 表达与 CTNNB1 突变存在之间的关系。 方法和结果：通过定量逆转录聚合酶链反应 (PCR) 检测 HCC 中 AMACR 和 GLUL（已确定的 β-catenin 下游靶标）的表达，并通过免疫组织化学检测其蛋白产物的表达。定量逆转录PCR分析显示，CTNNB1突变的HCC中AMACR的表达显着高于突变阴性的HCC或正常肝脏，与GLUL的表达一样。免疫组织化学还表明，AMACR 蛋白的强表达与 CTNNB1 突变的存在密切相关。 CTNNB1突变和AMACR过表达的HCC频繁产生胆汁。结论：AMACR过表达与HCC中CTNNB1突变的存在密切相关。 AMACR 是 β-连环蛋白的推定靶标，也是具有 CTNNB1 突变的 HCC 的出色免疫组织化学可检测标记物。由于 AMACR 在生理上参与胆汁酸合成，目前的观察表明 β-连环蛋白在胆汁酸代谢中具有调节作用。
Aims:alpha-Methylacyl-CoA racemase (AMACR) is expressed in the majority of hepatocellular carcinomas (HCCs) at variable levels, but the significance of AMACR overexpression remains elusive. The aim of this study was to investigate the relationship between AMACR expression and the presence of CTNNB1 mutations in HCCs.Methods and results:The expression of AMACR and GLUL, an established downstream target of beta-catenin was examined in HCCs, by quantitative reverse transcription polymerase chain reaction (PCR), and the expression of their protein products by immunohistochemistry. The quantitative reverse transcription PCR analysis showed that the expression of AMACR was significantly higher in HCCs with CTNNB1 mutations than in mutation-negative HCCs or normal livers, like the expression of GLUL. Immunohistochemistry also showed that strong AMACR protein expression was closely correlated with the presence of CTNNB1 mutations. HCCs with CTNNB1 mutations and those with AMACR overexpression frequently exhibited bile production.Conclusions:The overexpression of AMACR was closely correlated with the presence of CTNNB1 mutations in HCCs. AMACR is a putative target of beta-catenin as well as an excellent immunohistochemically detectable marker of HCCs with CTNNB1 mutations. As AMACR is physiologically involved in bile acid synthesis, the current observation implies a regulatory role of beta-catenin in bile acid metabolism.