Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-cripto-1 transgenic mice
Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-cripto-1 transgenic mice
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DOI：
10.1002/jcp.20062
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发表时间：
2004-11-01
影响因子：
5.6
通讯作者：
Salomon, DS
中科院分区：
文献类型：
--
作者：
Strizzi, L;Bianco, C;Salomon, DS
上皮-间质转化（EMT）促进上皮肿瘤细胞的迁移和侵袭。Cripto-1（CR-1）是表皮生长因子-CFC蛋白家族的成员，在体外增加细胞的迁移。在此，通过MMTV启动子（MMTV-CR-1）表达人CR-1转基因小鼠的乳腺增生和肿瘤以及过表达CR-1的小鼠乳腺上皮细胞系HC-11（HC-11/CR-1），评估了EMT特征性分子标志物和信号分子的表达。Western blot分析显示，在MMTV-CR-1肿瘤和HC-11/CR-1细胞中，E-钙粘蛋白的表达降低。N-cadherin、vimentin、cyclin-D1和锌指转录因子snail的表达在MMTV-CR-1肿瘤中增加。在HC-11/CR-1细胞中也发现snail mRNA的增加。在MMTV-CR-1肿瘤中，磷酸化（N-c-Src）、P-粘着斑激酶（FAK）、P-Akt、P-糖原合成酶激酶30（GSK-3 β）、去磷酸化（DP）-β-连环蛋白和各种整合素（如α 3、α v、β 1、β 3和β 4）的表达也增加。免疫组化显示MMTV-CR-1肿瘤切片中波形蛋白、N-钙粘蛋白、细胞周期蛋白-D1、平滑肌肌动蛋白、纤维连接蛋白、snail和β-连环蛋白阳性染色。用c-Src抑制剂PP 2处理的HC-11/CR-1细胞减少了P-c-Src和P-FAK、P-Akt、P-GSK-3 β、DP-β-连环蛋白的表达，所有这些已知都被c-Src激活。PP 2处理也减少了HC-1 I/CR-1细胞的迁移。这些结果表明，CR-1可能在促进EMT相关标志物和信号分子表达增加中起重要作用。(C)2004 Wiley-Liss，Inc.
Epithelial-mesenchymal transition (EMT) facilitates migration and invasion of epithelial tumor cells. Cripto-1 (CR-1), a member of the epidermal growth factor-CFC protein family increases migration of cells in vitro. Here the expression of molecular markers and signaling molecules characteristic of EMT were assessed in mammary gland hyperplasias and tumors from mice expressing the human CR-1 transgene by the MMTV promoter (MMTV-CR-1) and in mouse mammary epithelial cell line HC-11 overexpressing CR-1 (HC-11/CR-1). Western blot analysis showed decreased expression of E-cadherin in MMTV-CR-1 tumors and in HC-11/CR-1 cells. The expression of N-cadherin, vimentin, cyclin-D1, and of the zinc-finger transcription factor, snail, was increased in MMTV-CR-1 tumors. Increased snail mRNA was also found in HC-11/CR-1 cells. Expression of phosphorylated (N-c-Src, P-focal adhesion kinase (FAK), P-Akt, P-glycogen synthease kinase 30 (GSK-3beta), dephosphorylated (DP)-beta-catenin, and various integrins such as, alpha 3, alpha v, beta 1, beta 3, and beta 4 was also increased in MMTV-CR-1 tumors. Immunohistochemistry showed positive staining for vimentin, N-cadherin, cyclin-D1, smooth muscle actin, fibronectin, snail, and beta-catenin in MMTV-CR-1 tumor sections. HC-11/CR-1 cells treated with the c-Src inhibitor PP2 reduced the expression of P-c-Src and of P-FAK, P-Akt, P-GSK-3beta, DP-beta-catenin all known to be activated by c-Src. Migration of HC-1I/CR-1 cells was also reduced by PP2 treatment. These results suggest that CR-1 may play a significant role in promoting the increased expression of markers and signaling molecules associated with EMT. (C) 2004 Wiley-Liss, Inc.