Sarrió David, Palacios José, Hergueta-Redondo Marta, Gómez-López Gonzalo, Cano Amparo, Moreno-Bueno Gema
Department of Biochemistry UAM, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain.
BMC Cancer. 2009 Mar 3;9:74. doi: 10.1186/1471-2407-9-74.
Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood.
To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation.
Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type.
E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.
钙黏蛋白-连环蛋白黏附复合体的改变参与肿瘤的起始、进展和转移。然而，不同类型钙黏蛋白在乳腺癌生物学中的功能意义仍知之甚少。
为比较E-钙黏蛋白和P-钙黏蛋白在浸润性乳腺癌中的功能作用，我们将这些分子稳定转染至MDA-MB-231细胞系，并研究它们对细胞运动性、侵袭及基因表达调控的影响。
E-钙黏蛋白和P-钙黏蛋白的表达均显著增加细胞聚集，并诱导细胞从成纤维细胞形态转变为上皮细胞形态。尽管这些钙黏蛋白的表达并未完全逆转MDA-MB-231细胞的间充质表型，但E-钙黏蛋白和P-钙黏蛋白均以相似的方式减少了成纤维细胞样细胞通过细胞外基质的迁移和侵袭。此外，对表达E-钙黏蛋白和P-钙黏蛋白后的MDA-MB-231细胞进行基因芯片表达分析发现，这些分子可激活导致基因表达发生显著变化的信号通路。尽管E-钙黏蛋白和P-钙黏蛋白诱导的表达模式相似性多于差异性，但40个基因因任一类型钙黏蛋白的表达而发生不同程度的修饰。
E-钙黏蛋白和P-钙黏蛋白对MDA-MB-231细胞的表型和侵袭行为具有相似的功能影响。此外，我们首次证明这些钙黏蛋白可在浸润性乳腺癌细胞中诱导共同和特定的基因表达程序。重要的是，这些已鉴定的基因是未来研究人乳腺癌中钙黏蛋白表达改变的功能后果的潜在靶点。
