Here weshow that siRNA-mediated silencing of p53 is sufficient to completely abrogatehypersensitivity not only to Cisplatin but also to non-genotoxic inducers of p53such as the Mdm2 antagonist Nutlin-3 and the proteasome inhibitor Bortezomib.The close relationship between p53 protein levels and induction of apoptosis islost upon short-term differentiation, indicating that this predominantpro-apoptotic function of p53 is unique in pluripotent embryonal carcinoma (EC)cells. Here, MDM2 is linked to embryonal carcinoma.