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; Yongmei Yin

doi:10.18632/oncotarget.9287

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

Journal article

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Peer reviewed

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

Oncotarget, Vol.7(24), pp.37177-37191

06/14/2016

DOI: 10.18632/oncotarget.9287

PMCID: PMC5095067

PMID: 27184007

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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.

Animals

Antigens, CD - metabolism

Biomarkers, Tumor - genetics

Biomarkers, Tumor - metabolism

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Cadherins - metabolism

Down-Regulation

Epithelial-Mesenchymal Transition - genetics

Female

Gene Expression Regulation, Neoplastic

Gene Knockdown Techniques

Humans

Immunohistochemistry

MCF-7 Cells

Mice

Mice, Inbred BALB C

Mice, Nude

Proto-Oncogene Proteins c-mdm2 - genetics

Proto-Oncogene Proteins c-mdm2 - metabolism

RNA, Messenger - metabolism

RNA, Small Interfering - genetics

Snail Family Transcription Factors - genetics

Snail Family Transcription Factors - metabolism

Tissue Array Analysis

Up-Regulation

Vimentin - metabolism

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo
Creators: Xiangdong Lu - Nanjing Medical University
Caiyun Yan - Nanjing Medical University
Yi Huang - Magee-Womens Research Institute
Dongmin Shi - Nanjing Medical University
Ziyi Fu - Nanjing Maternity and Child Health Care Hospital
Jinrong Qiu - Nanjing Medical University
Yongmei Yin - Nanjing Medical University
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(24), pp.37177-37191
DOI: 10.18632/oncotarget.9287
PMID: 27184007
PMCID: PMC5095067
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Language: English
Date published: 06/14/2016
Academic Unit: Internal Medicine
Record Identifier: 9984383316802771

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