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

Sang Hyun Lee, George Poulogiannis, Saumyadipta Pyne, Shidong Jia, Lihua Zou, Sabina Signoretti, Massimo Loda, Lewis Clayton Cantley, Thomas M. Roberts

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11002-11007
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number24
DOIs
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • General

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