Inactivation of Tp53 and Pten drives rapid development of pleural and peritoneal malignant mesotheliomas.

ABSTRACT: Malignant mesothelioma (MM) is a therapy-resistant cancer arising primarily from the lining of the pleural and peritoneal cavities. The most frequently altered genes in human MM are cyclin-dependent kinase inhibitor 2A (CDKN2A), which encodes components of the p53 (p14ARF) and RB (p16INK4A) pathways, BRCA1-associated protein 1 (BAP1), and neurofibromatosis 2 (NF2). Furthermore, the p53 gene (TP53) itself is mutated in ~15% of MMs. In many MMs, the PI3K-PTEN-AKT-mTOR signaling node is hyperactivated, which contributes to tumor cell survival and therapeutic resistance. Here, we demonstrate that the inactivation of both Tp53 and Pten in the mouse mesothelium is sufficient to rapidly drive aggressive MMs. Pten^L/L ;Tp53^L/L mice injected intraperitoneally or intrapleurally

SUBMITTER: Sementino E 

PROVIDER: S-EPMC6168364 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature