This expression profile is associated with poor overall survival and short metastasis-free survival in patients with NSCLC. wtp53 upregulates MDM2 and forms a wtp53-MDM2-Slug complex that facilitates MDM2-mediated Slug degradation.
Therefore, the SNP in p73 G4C14-A4T14 and the MDM2 309 polymorphism may be markers of genetic susceptibility to NSCLC in a Chinese population, and there is a possible gene-gene interaction involved in the incidence of NSCLC.
The triazine-modified dendrimer efficiently stimulates the down-regulation of MDM2 gene in NSCLC PC9 cells, which induces significant cell apoptosis through the activation of apoptosis markers such as caspase-8 and poly(ADP-ribose) polymerase (PARP) cleavage.
Since mdm2 is capable of forming tight complexes with p53, possibly stabilizing it, our results suggest that this event may take place in a low percentage of NSCLC.
Our findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology.
The meta-analysis provides convincing evidence that the MDM2 T309 G polymorphism may contribute to NSCLC susceptibility, especially for Asians and women.
Interestingly, a highly significant inverse relationship was detected between p14(ARF) loss and Mdm2 overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P<0.0001).