TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer

Transcriptomic analysis of p53-wildtype and -mutant murine PDAC cells in the presence and absence of EZH2 revealed p53-status determined EZH2-dependent target gene regulation. We found that among others p53-pathway and apoptosis-related gene sets are enriched in p53wt PDAC cells upon EZH2 depletion but not in cells bearing a mutation in the Trp53 gene. mRNA expression profiles of murine p53wt (KrasG12D (KC), caNFATc1;KrasG12D (NKC)) and p53mut (KrasG12D;Trp53R173H/+ (KPC), KrasG12D;caNFATc1;Trp53R173H/+ (KNPC)) PDAC cells upon siRNA- (KC, KPC, KNPC) or shRNA- (NKC) mediated knockdown of EZH2 (48h)