Dissecting the role of PI3K activation in malignant mesothelioma development

Purpose: The PI3K/AKT/mTOR pathway is activated in most MM. In MM the mechanism of this pathway activation has not been completely elucidated, although loss of expression of PI3K pathway regulator, PTEN, is a frequent event in MM. Pten;Trp53 combined genetic loss in mouse mesothelium leads to non-epithelioid MM development. We assessed more broadly the impact of PI3K activation in MM development by comparing the effects of Pik3ca activation versus Pten inactivation in combination with Trp53 deletion on MM development. RNAseq was performed from tumor samples derived from Ptenlox/lox ; Trp53lox/lox and Pik3caH1047R/+; Trp53lox/lox mice derived sarcomatoid MM. Results: Our data also reveal that Pten loss has stronger oncogenic properties than Pik3ca mutation in MM. Overall design: Peritoneal MM developed in Ptenlox/lox;Trp53lox/lox and Pik3caH1047R/+;Trp53lox/lox mice following inoculation of adenoviruses coding for Cre-recombinase into the bladder wall. Mice were sacrificed at humane endpoint and tumors collected for further analysis