PTEN-regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression.

ABSTRACT: PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/Rb^PE:-/- mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas Rb^PE:-/- mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110β and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4,

SUBMITTER: Miller KA 

PROVIDER: S-EPMC10766561 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature