Title | A constitutively activated form of the p110beta isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Lee SHyun, Poulogiannis G, Pyne S, Jia S, Zou L, Signoretti S, Loda M, Cantley LClayton, Roberts TM |
Journal | Proc Natl Acad Sci U S A |
Volume | 107 |
Issue | 24 |
Pagination | 11002-7 |
Date Published | 2010 Jun 15 |
ISSN | 1091-6490 |
Keywords | Age Factors, Animals, Class I Phosphatidylinositol 3-Kinases, Disease Models, Animal, Enzyme Activation, Gene Expression Profiling, Genes, myc, Humans, Male, Metaplasia, Mice, Mice, Knockout, Mice, Transgenic, NF-kappa B, Phosphatidylinositol 3-Kinases, Prostate, Prostatic Intraepithelial Neoplasia, Prostatic Neoplasms, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Recombinant Fusion Proteins, Signal Transduction, Species Specificity |
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. |
DOI | 10.1073/pnas.1005642107 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 20534477 |
Grant List | P01CA089021 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.