Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primaryliver tumors with β-catenin mutations
Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primaryliver tumors with β-catenin mutations
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DOI：
10.1038/sj.onc.1208860
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发表时间：
2006-01-01
期刊：
影响因子：
8
通讯作者：
Perret, C
中科院分区：
文献类型：
--
作者：
Cavard, C;Terris, B;Perret, C
Wnt/β-catenin信号通路在许多人肝细胞癌（HCC）中被激活。我们试图通过β-连环蛋白的突变来确定参与肝癌发生和发展的基因。我们使用基于PCR的消减杂交技术比较了在已存在的β-连环蛋白激活的腺瘤中发生的人类HCC的恶性和良性成分之间的基因表达。其中两个基因属于再生基因（REG）家族。它们编码再生胰岛衍生的3 α（REG 3A/HIP/PAP/ REG-III）和1 α（REG 1A）蛋白，两者都参与肝脏和胰腺的再生和增殖。使用针对β-连环蛋白的siRNA，我们证明REG 3A是Huh 7肝癌细胞中β-连环蛋白信号传导的靶点。REG 3A和REG 1A表达的上调与42例HCC和28例肝母细胞瘤中的β-连环蛋白状态显著相关，其特征在于它们的β-连环蛋白状态。因此，我们报告了强有力的证据表明，这两个基因是在肝脏肿瘤发生Wnt通路的下游目标。
The Wnt/beta-catenin signaling pathways activated in many human hepatocellular carcinomas (HCC). We tried to identify the genes involved in carcinogenesis and progression of HCC with beta-catenin mutations. We used PCR-based subtractive hybridization to compare gene expression between malignant and benign components of a human HCC occurring in pre-existing adenoma activated for beta-catenin. Two of the genes identified belong to the Regenerating gene (REG) family. They encode the Regenerating islet-derived 3 alpha (REG3A/HIP/PAP/ REG-III) and 1 alpha (REG1A) proteins, both involved in liver and pancreatic regeneration and proliferation. Using siRNA directed against beta-catenin, we demonstrated that REG3A is a target of beta-catenin signaling in Huh7 hepatoma cells. The upregulation of REG3A and REG1A expression is significantly correlated to the beta-catenin status in 42 HCC and 28 hepatoblastomas characterized for their b-catenin status. Thus, we report strong evidence that both genes are downstream targets of the Wnt pathway during liver tumorigenesis.