Takayama T, Shiozaki H, Shibamoto S, Oka H, Kimura Y, Tamura S, Inoue M, Monden T, Ito F, Monden M
Department of Surgery II, Osaka University Medical School, Japan.
Am J Pathol. 1996 Jan;148(1):39-46.
Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including alpha- and beta-catenin. Although we previously demonstrated that alpha-catenin is crucial for cadherin function in vivo, little is known about the role of beta-catenin. We examined the expression of beta-catenin in human carcinoma samples along with normal tissue (esophagus, stomach, and colon) by immunostaining using our antibody for beta-catenin. Normal epithelium strongly expressed beta-catenin. However, beta-catenin expression was frequently reduced in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta-catenin forms a complex with E-cadherin not only in the normal epithelium but also in cancerous tissues. In coexpression patterns of E-cadherin and beta-catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules, whereas the other 13 tumors (23%) showed positive staining for E-cadherin and reduced expression of beta-catenin. These findings suggest that beta-catenin forms a complex with E-cadherin in vivo and down-regulation of beta-catenin expression is associated with malignant transformation.
组织中的细胞间黏附主要由钙黏蛋白分子的同型相互作用调节,这些分子通过包括α-连环蛋白和β-连环蛋白在内的细胞质蛋白锚定到细胞骨架上。尽管我们之前证明α-连环蛋白在体内对钙黏蛋白功能至关重要,但关于β-连环蛋白的作用知之甚少。我们使用针对β-连环蛋白的抗体,通过免疫染色检查了β-连环蛋白在人癌组织样本以及正常组织(食管、胃和结肠)中的表达。正常上皮细胞强烈表达β-连环蛋白。然而,β-连环蛋白的表达在食管癌原发肿瘤(15例中的10例,67%)、胃癌(19例中的9例,47%)和结肠癌(22例中的11例,50%)中经常降低。通过免疫沉淀研究,我们发现β-连环蛋白不仅在正常上皮细胞中,而且在癌组织中都与E-钙黏蛋白形成复合物。在E-钙黏蛋白和β-连环蛋白的共表达模式中,56个肿瘤中有43个(77%)显示这两种分子的表达相似,而另外13个肿瘤(23%)显示E-钙黏蛋白染色阳性且β-连环蛋白表达降低。这些发现表明β-连环蛋白在体内与E-钙黏蛋白形成复合物,β-连环蛋白表达的下调与恶性转化有关。