GSK-3β phosphorylation and alteration of β-catenin in hepatocellular carcinoma
GSK-3β phosphorylation and alteration of β-catenin in hepatocellular carcinoma
复制标题
DOI：
10.1016/s0304-3835(03)00421-x
复制
发表时间：
2003-09-25
期刊：
影响因子：
9.7
通讯作者：
Seow, HF
中科院分区：
文献类型：
--
作者：
Ban, KC;Singh, H;Seow, HF
本研究的目的是探讨磷酸化糖原合成酶激酶-3 β（phospho-GSK-3 beta）和β-catenin的表达与β-catenin基因GSK-3 β磷酸化位点突变之间的潜在相关性。这种方法的原因是为了更好地了解马来西亚肝癌发生的分子机制。应用免疫组织化学方法检测23例肝细胞癌（HCC）及癌旁组织中磷酸化GSK-3 β和β-catenin的表达及β-catenin的突变情况。磷酸化GSK-3 β和β-catenin在HCC组织中分别有12/23（52.2%）和13/23（56.5%）的表达，在癌旁组织中分别有6/23（26.1%）和9/23（39.1%）的表达。与周围肝组织相比，HCC组织中β-连环蛋白的过表达被发现在HCC组织中更高（p = 0.015）。此外，我们发现磷酸化GSK-3 β的表达与周围组织中β-catenin的积聚有关（p < 0.05）。首次报道磷酸化GSK-3 β的表达及其与HCC发生发展的关系。此外，这是马来西亚首次报道，在所有23对HCC和周围组织中，β-catenin基因上GSK-3 β共有磷酸化位点没有突变。这一结果不同于高黄曲霉毒素暴露地理区域的HCC。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p = 0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p < 0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure. (C) 2003 Elsevier Ireland Ltd. All rights reserved.