An in vivo study of Cdh1/APC in breast cancer formation.
An in vivo study of Cdh1/APC in breast cancer formation.
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DOI：
10.1002/ijc.24399
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
Fujita T;Liu W;Doihara H;Wan Y
泛素-蛋白酶体系统(UPS)的失调与多种类型的肿瘤发生有关。我们以前的研究已经表明，CDH1/APC可能通过调控Skp2-p27-cyclinE/CDK2轴来调节肿瘤的形成。在这项工作中，我们利用异种移植的小鼠乳腺癌模型来确定CDH1/APC在体内潜在地抑制肿瘤生长的机制。在此，我们报告了CDH1的缺失会显著促进乳腺肿瘤的增殖，而CDH1的升高则会抑制乳腺肿瘤的生长。对乳腺组织阵列的分析表明，正常乳腺组织中CDH1水平较高，而Skp2表达较低，p27水平较高。相反，乳腺癌组织中CDH1和p27染色阳性的百分比随着Skp2水平的升高而显著降低。因此，E3连接酶CDH1/APC可能通过调节Skp2-p27介导的细胞周期进程来抑制乳腺肿瘤的生长。
Dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in several types of tumorigenesis. Our previous studies have shown the potential role of Cdh1/APC in regulating tumor formation via governing the Skp2-p27-cyclinE/CDK2 axis. In this work, we utilized a xenograft mouse breast cancer model to identify the mechanism by which Cdh1/APC potentially suppresses tumor growth in vivo. Here, we report that depletion of Cdh1 results in a significant enhancement of the breast tumor proliferation, while elevated Cdh1 leads to suppression of breast tumor growth. Analysis of breast tissue arrays has indicated that higher levels of Cdh1 are associated with normal breast epithelial tissues whereas lower Skp2 expression and elevated p27 levels are detected. Conversely, the percentage of breast cancer tissues stained positive for Cdh1 and p27 are significantly lower with higher Skp2 levels. Thus, the E3 ligase, Cdh1/APC, may inhibit breast tumor growth via regulating Skp2-p27 mediated cell cycle progression.
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