Giroldi L A, Bringuier P P, Shimazui T, Jansen K, Schalken J A
Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Int J Cancer. 1999 Jul 2;82(1):70-6. doi: 10.1002/(sici)1097-0215(19990702)82:1<70::aid-ijc13>3.0.co;2-#.
We are investigating the hypothesis that cancer progression involves the formation of abnormal cadherin-catenin complexes. The detailed analysis of cadherins and catenins expressed in a panel of 17 human bladder-cancer cell lines revealed that E-cadherin was down-regulated at the mRNA level in 5 cell lines. Interestingly, plakoglobin was also down-regulated at the mRNA level in these 5 cell lines only. Furthermore, a slower migrating form of pp120 was detected in these cell lines and in 2 cell lines with heterogeneous E-cadherin expression. Cloning of the cadherins expressed in the bladder lines revealed that P-cadherin is expressed in the lines expressing E-cadherin and down-regulated at the mRNA level in lines devoid of E-cadherin. N-cadherin was expressed in the 5 lines with reduced E-cadherin expression, in the 2 lines with heterogeneous E-cadherin expression and in 2 other cell lines. Thus, we showed that catenin changes occur in correlation with lack of E-cadherin expression and that N-cadherin becomes predominantly expressed in cells that have lost E-cadherin expression. Our data suggest that co-regulation of the expression of genes encoding different members of the classical cadherins occurs during tumor progression and that expression of some catenins is also coordinated with cadherin expression.
我们正在研究癌症进展涉及异常钙黏蛋白 - 连环蛋白复合物形成的假说。对17种人膀胱癌细胞系中表达的钙黏蛋白和连环蛋白进行的详细分析表明,5种细胞系中E - 钙黏蛋白在mRNA水平下调。有趣的是,仅在这5种细胞系中,桥粒芯蛋白在mRNA水平也下调。此外,在这些细胞系以及2种E - 钙黏蛋白表达异质性的细胞系中检测到迁移较慢的pp120形式。对膀胱癌细胞系中表达的钙黏蛋白进行克隆显示,P - 钙黏蛋白在表达E - 钙黏蛋白的细胞系中表达,而在缺乏E - 钙黏蛋白的细胞系中mRNA水平下调。N - 钙黏蛋白在5种E - 钙黏蛋白表达降低的细胞系、2种E - 钙黏蛋白表达异质性的细胞系以及另外2种细胞系中表达。因此,我们表明连环蛋白变化与E - 钙黏蛋白表达缺失相关,并且N - 钙黏蛋白在失去E - 钙黏蛋白表达的细胞中占主导地位表达。我们的数据表明,在肿瘤进展过程中,编码经典钙黏蛋白不同成员的基因表达存在共同调节,并且一些连环蛋白的表达也与钙黏蛋白表达协调一致。