Journal
ONCOTARGET
Volume 7, Issue 24, Pages 37177-37191Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9287
Keywords
breast cancer; MDM2; epithelial-mesenchymal transition; Snail
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Funding
- National Natural Science Foundation of China [81172503]
- Jiangsu Province Clinical Science and Technology Projects (clinical research center) [BL 2012008]
- Provincial Initiative Program for Excellency Disciplines, Jiangsu Province, China
- Jiangsu Healthy Major Project [RC01153]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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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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