Instituto de Biología y Medicina Experimental, National Research Council of Argentina (CONICET), C1428ADN Buenos Aires, Argentina.
J Cell Physiol. 2010 Mar;222(3):596-605. doi: 10.1002/jcp.21974.
Epithelial cadherin (E-cadherin) is a 120 kDa cell-cell adhesion molecule involved in the establishment of epithelial adherens junctions. It is connected to the actin cytoskeleton by adaptor proteins such as beta-catenin. Loss of E-cadherin expression/function has been related to tumor progression and metastasis. Several molecules associated with down-regulation of E-cadherin have been described, within them neural cadherin, Twist and dysadherin. Human breast cancer cell lines IBH-6 and IBH-4 were developed from ductal primary tumors and show characteristic features of malignant epithelial cells. In this study expression of E-cadherin and related proteins in IBH-6 and IBH-4 cell lines was evaluated. In IBH-6 and IBH-4 cell extracts, only an 89 kDa E-cadherin form (Ecad89) was detected, which is truncated at the C-terminus and is present at low levels. Moreover, no accumulation of the 86 kDa E-cadherin ectodomain and of the 38 kDa CTF1 fragment was observed. IBH-6 and IBH-4 cells showed an intracellular scattered E-cadherin localization. beta-catenin accompanied E-cadherin localization, and actin stress fibers were identified in both cell types. E-cadherin mRNA levels were remarkably low in IBH-6 and IBH-4 cells. The E-cadherin mRNA and genomic sequence encoding exons 14-16 could not be amplified in either cell line. Neither the mRNA nor the protein of neural cadherin and dysadherin were detected. Up-regulation of Twist mRNA was found in both cell lines. In conclusion, IBH-6 and IBH-4 breast cancer cells show down-regulation of E-cadherin expression with aberrant protein localization, and up-regulation of Twist; these features can be related to their invasive/metastatic characteristics.
上皮钙黏蛋白（E-cadherin）是一种 120 kDa 的细胞-细胞黏附分子，参与上皮细胞黏附连接的形成。它通过衔接蛋白如β-连环蛋白与肌动蛋白细胞骨架相连。E-cadherin 表达/功能的丧失与肿瘤的进展和转移有关。已经描述了几种与 E-cadherin 下调相关的分子，包括神经钙黏蛋白、Twist 和黏附素。人乳腺癌细胞系 IBH-6 和 IBH-4 是从导管原发性肿瘤中开发的，表现出恶性上皮细胞的特征。在这项研究中，评估了 IBH-6 和 IBH-4 细胞系中 E-cadherin 和相关蛋白的表达。在 IBH-6 和 IBH-4 细胞提取物中，仅检测到 C 端截断且低水平表达的 89 kDa E-cadherin 形式（Ecad89）。此外，未观察到 86 kDa E-cadherin 胞外域和 38 kDa CTF1 片段的积累。IBH-6 和 IBH-4 细胞显示 E-cadherin 在内质网中的点状定位。β-连环蛋白伴随着 E-cadherin 的定位，两种细胞类型都有肌动蛋白应力纤维。IBH-6 和 IBH-4 细胞的 E-cadherin mRNA 水平显著降低。在两种细胞系中都无法扩增编码外显子 14-16 的 E-cadherin mRNA 和基因组序列。未检测到神经钙黏蛋白和黏附素的 mRNA 和蛋白。在两种细胞系中均发现 Twist mRNA 的上调。总之，IBH-6 和 IBH-4 乳腺癌细胞表现出 E-cadherin 表达下调，伴有异常蛋白定位和 Twist 上调；这些特征可能与其侵袭/转移特性有关。
