PTEN loss and activation of K-RAS and β-catenin cooperate to accelerate prostate tumourigenesis.

ABSTRACT: Aberrant phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) and WNT signalling are emerging as key events in the multistep nature of prostate tumourigenesis and progression. Here, we report a compound prostate cancer murine model in which these signalling pathways cooperate to produce a more aggressive prostate cancer phenotype. Using Cre-LoxP technology and the probasin promoter, we combined the loss of Pten (Pten^fl/fl ), to activate the PI3K signalling pathway, with either dominant stabilized β-catenin [Catnb^+/lox(ex3) ] or activated K-RAS (K-Ras^+/V12 ) to aberrantly activate WNT and MAPK signalling, respectively. Synchronous activation of all three pathways (triple mutants) significantly reduced survival (median 96 days) as compare

SUBMITTER: Jefferies MT 

PROVIDER: S-EPMC6128396 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature