Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo

被引:29
|
作者
Lu, Xiangdong [1 ]
Yan, Caiyun [1 ]
Huang, Yi [2 ]
Shi, Dongmin [1 ]
Fu, Ziyi [3 ]
Qiu, Jinrong [1 ]
Yin, Yongmei [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Jiangsu, Peoples R China
[2] Univ Pittsburgh, Magee Womens Res Inst, Dept Pharmacol & Chem Biol, Inst Canc, Pittsburgh, PA USA
[3] Nanjing Med Univ, Affiliated Nanjing Matern & Child Hlth Care Hosp, Nanjing Maternal & Child Med Inst, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
breast cancer; MDM2; epithelial-mesenchymal transition; Snail; E-CADHERIN; RESISTANCE; PATHWAY; GENE; EMT; P53;
D O I
10.18632/oncotarget.9287
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers. In this study, we investigated the role of MDM2 in epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms in breast cancer cells in vitro and in vivo. The results showed that up-regulation of MDM2 in MCF-7 cells altered the cell morphology to a mesenchymal phenotype. Knockdown of MDM2 in MDA-MB-231 cells altered the cell morphology to the epithelial phenotype. In addition, overexpression of MDM2 increased the expression of N-cadherin and Vimentin and decreased the expression of E-cadherin, at both the mRNA and protein levels, in vitro and in vivo. Conversely, down-regulation of MDM2 decreased the expression of N-cadherin and Vimentin, and increased the expression of E-cadherin in vitro. Furthermore, MDM2 up-regulated both the mRNA and protein expression of Snail in vitro and in vivo. Knockdown of Snail almost abolished MDM2 induced EMT in vitro. Finally, we found that MDM2 expression correlated with EMT markers and Snail: Snail expression was inversely associated with E-cadherin in human breast cancer samples. Our findings demonstrated that MDM2 induces EMT by enhancing Snail expression in vitro and in vivo. Thus, MDM2 may be a potential target for therapy against human metastatic breast cancer.
引用
收藏
页码:37177 / 37191
页数:15
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