MDM2 is overexpressed and regulated by the eukaryotic translation initiation factor 4E (eIF4E) in human squamous cell carcinoma of esophagus.

Background: We investigated the association between the increased eukaryotic translation initiation factor 4E (eIF4E) level and MDM2 overexpression in the esophageal cancer tissue and cells.

Methods: This was a retrospective study of specimens from esophageal cancer patients treated over a 5-year period in a Taiwan university hospital. The predictor variable was eIF4E level in esophageal tumors and CE48T/VGH and TE6 esophageal carcinoma cell lines.

Rapamycin increases the p53/MDM2 protein ratio and p53-dependent apoptosis by translational inhibition of mdm2 in cancer cells.

Rapamycin, a potential anti-cancer agent, modulates activity of various factors functioning in translation, including eIF4E, an initiation factor selectively regulating expression of a subset of cellular transcripts. We show here that rapamycin suppresses levels of the p53-regulator MDM2 by translational inhibition without affecting mdm2 mRNA expression or protein stability. Rapamycin inhibits translation of mdm2 mRNA from the constitutive P1 promoter, which contains two upstream ORFs (uORFs) in the 5'UTR.