Qiao Q, Ramadani M, Gansauge S, Gansauge F, Leder G, Beger H G
Department of General Surgery, First Teaching Hospital of Beijing Medical University, Beijing, P. R. China.
Int J Cancer. 2001 May 20;95(3):194-7. doi: 10.1002/1097-0215(20010520)95:3<194::aid-ijc1033>3.0.co;2-m.
Beta-catenin is a component of the E-cadherin-catenin cell adhesion complex. It plays also a role in intracellular signaling and can function as an oncogene when it binds to the T-cell factor 4 (Tcf4)-binding site in the promoter region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of beta-catenin in relationship with cyclin D1 overexpression, tumor grade, clinicopathologic parameters and patients' survival in 43 ductal adenocarcinomas of the pancreas and 5 normal pancreatic tissues. We were able to show that, both reduced membranous beta-catenin expression (25 of 43, 58.1%) and accumulation of beta-catenin in the cytoplasm (28 of 43, 65.1%) correlated significantly with cyclin D1 overexpression (both p < 0.0005). Furthermore, we could show a clear correlation between reduced membranous expression and ectopic cytoplasmic expression of beta-catenin (p < 0.0005). Among patients with carcinomas showing no cytoplasmic expression, the 1-year survival was 86.6% whereas among patients with carcinomas showing cytoplasmic expression only 35.7% survived 1 year (p < 0.01). Co-precipitation experiments revealed reduced beta-catenin bound to the E-cadherin-catenin complex in pancreatic tumor tissues compared with normal pancreatic tissues. These results suggest that beta-catenin may be involved in the tumorigenesis of pancreatic cancer and exhibited its effects mainly by the transactivation of cyclin D1.
β-连环蛋白是E-钙黏蛋白-连环蛋白细胞黏附复合物的一个组成部分。它在细胞内信号传导中也发挥作用，当它与细胞周期蛋白D1启动子区域的T细胞因子4（Tcf4）结合位点结合并转移至细胞核后激活基因时，可作为一种癌基因发挥作用。我们评估了43例胰腺导管腺癌和5例正常胰腺组织中β-连环蛋白的免疫组化表达模式，及其与细胞周期蛋白D1过表达、肿瘤分级、临床病理参数和患者生存率的关系。我们发现，膜性β-连环蛋白表达降低（43例中的25例，58.1%）和β-连环蛋白在细胞质中积聚（43例中的28例，65.1%）均与细胞周期蛋白D1过表达显著相关（均p<0.0005）。此外，我们还发现β-连环蛋白膜性表达降低与异位细胞质表达之间存在明显相关性（p<0.0005）。在癌组织无细胞质表达的患者中，1年生存率为86.6%，而在癌组织仅显示细胞质表达的患者中，1年生存率仅为35.7%（p<0.01）。共沉淀实验显示，与正常胰腺组织相比，胰腺肿瘤组织中与E-钙黏蛋白-连环蛋白复合物结合的β-连环蛋白减少。这些结果表明，β-连环蛋白可能参与胰腺癌的肿瘤发生，并主要通过激活细胞周期蛋白D1发挥作用。
