Rabbit Anti-Human MDM2 monoclonal antibody, clone 5I37M5

Glioblastoma is the most common malignant primary brain tumor among adults and one of the most lethal cancers. It is characterized by the deregulation of signaling pathways involving proliferation, growth, survival, and other factors. MicroRNAs (miRNAs) play a role in the regulation of genes by affecting the 3' untranslated region (UTR) of mRNA and affect many cell functions. The present study showed that miR-129 decreased the expression of retinoblastoma and p53 signaling pathways' genes, including CDK4, CDK6, and MDM2. The real-time PCR data indicated that expression of CDK4 in U251 and U87 cell lines declined by 69.8% and 47% (p < 0.05), respectively, and expression of CDK6 and MDM2 in U251 cells decreased by 55.3% (p < 0.0001) and 34.7% (p < 0.05), respectively. Luciferase assays confirmed that overexpression of miR-129 decreased the expression of the CDK4 gene by 58.9% (p < 0.01), CDK6 by 35.7% (p < 0.0001), and MDM2 by 49% (p < 0.001). Moreover, cell cycle assays showed a decrease of the G(2)-phase population to 10% and pre-G(2) arrest in U87 cells (p < 0.05). Additionally, wound healing assays indicated that miR-129 overexpression inhibits cell growth of glioblastoma cells. These findings introduced novel targets for miR-129 in glioblastoma cells.

Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lackingMDM2gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression withoutMDM2gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.