The up-regulation of proteasome subunits and lysosomal proteases in hepatocellular carcinomas of the HBx gene knockin transgenic mice
The up-regulation of proteasome subunits and lysosomal proteases in hepatocellular carcinomas of the HBx gene knockin transgenic mice
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DOI：
10.1002/pmic.200500218
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发表时间：
2006-01-01
期刊：
影响因子：
3.4
通讯作者：
Yang, X
中科院分区：
文献类型：
--
作者：
Cui, F;Wang, YL;Yang, X
B肝炎病毒（HBV）慢性感染已被证实是肝细胞癌（HCC）的重要危险因素之一。HBx已被证明在病毒生命周期和HCC的发展中起作用。最近，我们报道通过基因敲入产生的HBx转基因小鼠（p21-HBx）在18月龄时发生HCC。为了进一步研究HBx在体内HCC发展过程中的功能，我们对转基因和野生型对照小鼠进行了蛋白质组学分析。2-DE结合MALDI-TOF MS分析显示，p21-HBx转基因小鼠肿瘤组织中蛋白酶体亚基（PSMA 6、PSMB 4、PSMC 2和PSMD 12）表达上调。参与细胞蛋白水解过程的组织蛋白酶B、泛喹啉-细胞色素C还原酶核心蛋白1和ATP依赖性酪蛋白分解蛋白酶在肿瘤中也被发现增加。RT-PCR结果在转基因小鼠肿瘤和人肝癌中得到证实。以上结果提示，泛素-蛋白酶体途径和溶酶体途径的增强可能参与了HBx相关性肝细胞癌的发生。
Chronic infection of hepatitis virus B (HBV) has been proven to be one of the most important risk factors of hepatocellular carcinoma (HCC). HBx has been shown to function in the viral life cycle and the development of HCC. Recently, we have reported that HBx transgenic mice (p21-HBx), generated by gene knockin, develop HCC at the age of 18 months. To further study the function of HBx during the development of HCC in vivo, we performed proteomic analysis of the transgenic and wild-type control mice. The combination of 2-DE and MALDI-TOF MS revealed that proteasome subunits (PSMA6, PSMB4, PSMC2 and PSMD12) were up-regulated in tumor tissues of the p21-HBx transgenic mice. Cathepsin B, ubiquinol-cytochrome C reductase core protein 1 and an ATP-dependent caseinolytic protease, which were involved in the cellular proteolytic process, were also found increased in tumors. The results were confirmed in tumors of transgenic mice and HCCs of human using RT-PCR. All these results suggested that the strengthened ubiquitin-proteasome and lysosomal pathway might contribute to the development of HBx-related H CC.