title: Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo.
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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Pharmacology and Chemical Biology, Magee Women's Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Shi
authors.affiliation: Nanjing Maternal and Child Medical Institute, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; Snail; breast cancer; epithelial-mesenchymal transition