Impact of MDM2 Oncogene on Epithelial–Mesenchymal Transition and Metastasis of Prostate Cancer Cells

Murine Double Minute 2 (MDM2) gene containing E3 ubiquitin ligase is overexpressed in nearly 40- 80% of late-stage metastatic cancers. MDM2 acts as a negative regulator of p53 by inhibiting its transcriptional activation and inducing proteasomal degradation by ubiquitination. Hence, MDM2 overexpression is often associated with increased Tumor Angiogenesis, Epithelial to Mesenchymal Transition (EMT), drug resistance, and aggressiveness. EMT is a morphologic cellular program simply defined as the phenotypic transition from an epithelial to a mesenchymal state, including gain of invasive and migratory properties, and thus, is critical for the conversion of early-stage tumors into metastatic malignancies. The primary focus of this study is to determine MDM2’s role in inducing EMTin prostate cancer cells. Preliminary studies were performed on LNCaP and MDM2 overexpressing LNCaP-MST cell lines. As expected, LNCaP-MST, which express tenfold higher levels of MDM2 as compared to LNCaP, was mesenchymal in phenotype. On the other hand, LNCaP was more epithelial- like as evidenced by the Western Blot analysis of some key epithelial and mesenchymal markers. Further experiments are underway to determine some of the underlying mechanisms mediated by MDM2 in inducing EMT (This project was supported by the Royal Dames of Cancer Research, Ft. Lauderdale, FL)