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

• DOI: 10.1073/pnas.1005642107
• Publication Date: 2010-06-02T00:51:16Z
• Authors: Sang Hyun Lee; George Poulogiannis; Saumyadipta Pyne; Shidong Jia; Lihua Zou; Sabina Signoretti; Massimo Loda; Lewis Clayton Can...; Thomas M. Roberts
• Keywords: Male; Mice, Knockout; Prostatic Intraepithelial Neoplasia; Metaplasia; 0303 health sciences; Class I Phosphatidylinositol 3-Kinases; Gene Expression Profiling; Age Factors; Genes, myc; NF-kappa B; PTEN Phosphohydrolase; Prostate; Prostatic Neoplasms; Mice, Transgenic; Enzyme Activation; Disease Models, Animal; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Animals; Humans; Proto-Oncogene Proteins c-akt

Recent work has shown that ablation of p110β, but not p110α, 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 p110β activation is necessary for tumorigenesis driven by PTEN loss. Given the multiple functions of PTEN, we wondered if p110β activation also is sufficient for tumorigenesis. Here, we report that transgenic expression of a constitutively activated p110β 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.