Pierceall W E, Woodard A S, Morrow J S, Rimm D, Fearon E R
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Oncogene. 1995 Oct 5;11(7):1319-26.
Alterations in intercellular junction and membrane cytoskeletal proteins may underlie some of the morphological, invasive and metastatic properties of cancer. E-cadherin, a transmembrane protein that functions in epithelial cell-cell interactions at adherens junctions, is linked to the membrane cytoskeletal matrix through interactions with alpha- and beta-catenin. We have carried out studies of E-cadherin and alpha- and beta-catenin in 18 breast cancer cell lines to determine the prevalence and nature of alterations in these genes in breast cancer. Ten lines failed to express E-cadherin protein at detectable levels and seven failed to produce detectable levels of E-cadherin transcripts. In a line lacking E-cadherin expression (SK-BR-3) a homozygous deletion of a large portion of the E-cadherin gene was noted. Localized sequence alterations in E-cadherin transcripts were not identified in any lines. In contrast to the results of a previous study, no relationship was identified between E-cadherin expression and HER-2/NEU expression. Two of the 18 lines had no detectable alpha-catenin protein and six others had reduced levels. The two lines lacking alpha-catenin protein had reduced or undetectable levels of alpha-catenin transcripts, while no consistent changes in alpha-catenin transcript levels were seen in the lines with reduced, but detectable, levels of alpha-catenin protein. Similarly, although two lines lacked beta-catenin protein, in most lines the levels of beta-catenin transcripts and protein were not well correlated with one another. Our findings suggest that alterations in E-cadherin and alpha- and beta-catenin expression are frequent in human breast cancer-derived cell lines, and that in some cases the decreased expression may result from mutations in the genes. Furthermore, the frequent alterations in the expression of these proteins argue that loss of function in the E-cadherin-catenin pathway may be critical in the development of many breast cancers.
细胞间连接和膜细胞骨架蛋白的改变可能是癌症某些形态学、侵袭性和转移性特性的基础。E-钙黏蛋白是一种跨膜蛋白，在黏附连接处的上皮细胞间相互作用中发挥作用，它通过与α-连环蛋白和β-连环蛋白相互作用与膜细胞骨架基质相连。我们对18种乳腺癌细胞系中的E-钙黏蛋白以及α-连环蛋白和β-连环蛋白进行了研究，以确定这些基因在乳腺癌中改变的普遍性和性质。10种细胞系未能在可检测水平表达E-钙黏蛋白蛋白，7种细胞系未能产生可检测水平的E-钙黏蛋白转录本。在一个缺乏E-钙黏蛋白表达的细胞系（SK-BR-3）中，发现E-钙黏蛋白基因的很大一部分存在纯合缺失。在任何细胞系中均未发现E-钙黏蛋白转录本的局部序列改变。与先前一项研究的结果相反，未发现E-钙黏蛋白表达与HER-2/NEU表达之间存在关联。18种细胞系中有2种未检测到α-连环蛋白蛋白，另外6种细胞系中的α-连环蛋白水平降低。缺乏α-连环蛋白蛋白的2种细胞系中α-连环蛋白转录本水平降低或无法检测到，而在α-连环蛋白蛋白水平降低但可检测到的细胞系中，未观察到α-连环蛋白转录本水平的一致变化。同样，尽管有2种细胞系缺乏β-连环蛋白蛋白，但在大多数细胞系中，β-连环蛋白转录本水平和蛋白水平之间的相关性并不好。我们的研究结果表明，E-钙黏蛋白以及α-连环蛋白和β-连环蛋白表达的改变在人乳腺癌来源的细胞系中很常见，并且在某些情况下，表达降低可能是由于基因突变所致。此外，这些蛋白表达的频繁改变表明，E-钙黏蛋白-连环蛋白途径的功能丧失可能在许多乳腺癌的发生发展中起关键作用。
