Single nucleotide polymorphisms in the promoter region of MDM2, as well as amplified MDM2 gene, have been observed in various malignant tumors, including breast cancer, lung cancer, esophageal cancer, colon cancer, and various sarcomas,41, 42 and antagonists of MDM2/MDMX can reactivate the p53 pathway and enhance the apoptosis of RB cells,43 while the high expression of MDMX and MDM2 subsequently inhibits the p53 pathway during tumor development.27 Here, MDM4 is linked to esophageal cancer.