Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma.

ABSTRACT:

Background

Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma.

Methodology/principal findings

We crossed mice with constitutive activation of Smoothened, SmoA1, with Pten deficient mice. Both constitutive and conditional Pten deficiency doubled the incidence of mice with symptoms of medulloblastoma and resulted in decreased survival. Analysis revealed a clear separation of gene signatures, with up-regulation of genes in the PI-3 kinase signaling pathway, including downstream activation of angiogenesis in SmoA1+/-; Pten +/- medulloblastomas. Western blotting and immunohistochemistry confirmed reduced or absent Pten, Akt activation, and increased angiogenesis in Pt

SUBMITTER: Castellino RC 

PROVIDER: S-EPMC2877103 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature