Oncotarget

Research Papers:

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

Xiangdong Lu _, Caiyun Yan, Yi Huang, Dongmin Shi, Ziyi Fu, Jinrong Qiu and Yongmei Yin

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Oncotarget. 2016; 7:37177-37191. https://doi.org/10.18632/oncotarget.9287

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Abstract

Xiangdong Lu1,*, Caiyun Yan1,*, Yi Huang2, Dongmin Shi1, Ziyi Fu3, Jinrong Qiu1, Yongmei Yin1

1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China

2Department of Pharmacology and Chemical Biology, Magee Women’s Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

3Nanjing Maternal and Child Medical Institute, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Yongmei Yin, email: [email protected]

Keywords: breast cancer, MDM2, epithelial-mesenchymal transition, Snail

Received: August 28, 2015    Accepted: April 22, 2016    Published: May 11, 2016

ABSTRACT

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.


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