Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis
Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis
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DOI：
10.1158/1078-0432.ccr-05-2245
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发表时间：
2006-09-15
影响因子：
11.5
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Shibata, Rie;Mori, Taisuke;Sakamoto, Michiie
目的：肝细胞癌（HCC）伴发慢性肝病是一种多阶段的肿瘤进展过程。我们先前在研究多阶段肝癌发生的表达谱时，确定热休克蛋白70为早期肝癌的分子标志物。在这份报告中，我们研究了环化酶相关蛋白2（CAP2），这也被列为在早期HCC中上调的基因。实验设计：我们通过实时定量PCR测量CAP2 mRNA的水平。结果：实时荧光定量PCR结果显示，与正常肝组织相比，早期肝癌组织中CAP2 mRNA表达水平明显上调，进展期肝癌组织中CAP2 mRNA表达进一步上调。我们提出了一个多克隆抗体CAP2，它显示了一个单一的53 kDa的强强度带在人肝癌细胞系和肝癌组织，但只有一个弱带在非癌肝组织中的Western印迹分析。CAP2的免疫组化检测显示其显着的过度表达在早期肝癌与非癌和癌前病变相比，并在进展性肝癌与早期hcoc.Conclusion：我们的研究结果表明，CAP2是上调肝癌与非癌和癌前病变相比。这是第一份证明CAP2在人类癌症中上调的报告，并且这可能与多阶段肝癌发生有关。
Purpose: Hepatocellular carcinoma (HCC) associated with chronic liver disease is known to show an obvious multistage process of tumor progression. We previously identified heat shock protein 70 as a molecular marker of early HCC during investigation of expression profiling in multistage hepatocarcinogenesis. In this report, we examined cyclase-associated protein 2 (CAP2), which is also listed as an up-regulated gene in early HCC.Experimental Design: We measured the level of CAP2 mRNA by real-time quantitative PCR. We raised a polyclonal antibody against CAP2 and we confirmed the expression of CAP2 by immunoblotting and immunohistochemistry in HCC cell lines and HCC tissues.Results: According to real-time quantitative PCR, the level of CAP2 mRNA was up-regulated in early HCC when compared with noncancerous liver tissue, and it was further up-regulated in progressed HCC. We raised a polyclonal antibody against CAP2, which showed a single 53-kDa band of strong intensity in the human HCC cell lines and HCC tissues but only a weak band in the noncancerous liver tissues in Western blot analysis. Immunohistochemical examination of CAP2 revealed its significant overexpression in early HCC when compared with noncancerous and precancerous lesions and in progressed HCC when compared with early HCC.Conclusion: Our findings show that CAP2 is up-regulated in HCC when compared with noncancerous and precancerous lesions. This is the first report that proves that CAP2 is up-regulated in human cancers and that this is possibly related to multistage hepatocarcinogenesis.