title: MDM2 and PSMA Play Inhibitory Roles in Metastatic Breast Cancer Cells Through Regulation of Matrix Metalloproteinases.
abstract: OBJECTIVE
  Mouse double minute 2 (MDM2) and prostate-specific membrane antigen (PSMA) are currently under investigation as individual therapeutic targets due to their overexpression in many cancer types, as well as their pro-tumorigenic effect on cells. Recently, knockdown of PSMA was linked to a decrease in MDM2 and matrix metalloproteinase 2 (MMP2) and an increase in MMP3 and MMP13 expression. We aimed to assess the link between PSMA, MDM2 and the MMPs in metastatic breast cancer cell lines.
  
  
  METHODS
  Real-time quantitative polymerase chain reaction (PCR) and western blotting were used to assess siRNA-mediated knockdown of MDM2 and PSMA in MDA-MB-231 and ZR-75.1 breast cancer cells. Assays to assess the growth, adhesion, migration and invasion of the cells following siRNA treatment were undertaken. MMP and tissue inhibitor of matrix metalloproteinases (TIMP) levels were assessed via quantitative PCR.
  
  
  RESULTS
  Knockdown of MDM2 resulted in a decrease in PSMA expression levels and vice versa; although this trend was not replicated at the protein level. Knockdown of each of the molecules resulted in a decrease in growth, adhesion, migration and invasive ability of breast cancer cells. Both knockdowns led to a decrease in MMP2 and an increase in MMP3, -10 and -13 gene expression.
  
  
  CONCLUSIONS
  MDM2 and PSMA may co-regulate the expression of certain MMPs and, thus, the functionality of cells in metastatic breast cancer.
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K. bradburyr@cf.ac.uk.
authors.forename: Robyn
authors.initials: R
authors.lastname: Bradbury
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Cui
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D000954:Antigens, Surface; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D020782:Matrix Metalloproteinases
keywords: MDM2; MMPs; PSMA; breast cancer; matrix metalloproteinases