A constitutively activated form of the p110β isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice Academic Article uri icon

Overview

MeSH Major

  • Phosphatidylinositol 3-Kinases
  • Prostatic Intraepithelial Neoplasia
  • Prostatic Neoplasms

abstract

  • Recent work has shown that ablation of p110beta, but not p110alpha, markedly impairs tumorigenesis driven by loss of phosphatase and tensin homolog (PTEN) in the mouse prostate. Other laboratories have reported complementary data in human prostate tumor lines, suggesting that p110beta activation is necessary for tumorigenesis driven by PTEN loss. Given the multiple functions of PTEN, we wondered if p110beta activation also is sufficient for tumorigenesis. Here, we report that transgenic expression of a constitutively activated p110beta allele in the prostate drives prostate intraepithelial neoplasia formation. The resulting lesions are similar to, but are clearly distinct from, the ones arising from PTEN loss or Akt activation. Array analyses of transcription in multiple murine prostate tumor models featuring PI3K/AKT pathway activation allowed construction of a pathway signature that may be useful in predicting the prognosis of human prostate tumors.

publication date

  • June 15, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2890726

Digital Object Identifier (DOI)

  • 10.1073/pnas.1005642107

PubMed ID

  • 20534477

Additional Document Info

start page

  • 11002

end page

  • 7

volume

  • 107

number

  • 24