Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.

TitleProstate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.
Publication TypeJournal Article
Year of Publication2003
AuthorsMajumder PK, Yeh JJen, George DJ, Febbo PG, Kum J, Xue Q, Bikoff R, Ma H, Kantoff PW, Golub TR, Loda M, Sellers WR
JournalProc Natl Acad Sci U S A
Volume100
Issue13
Pagination7841-6
Date Published2003 Jun 24
ISSN0027-8424
KeywordsAnimals, Enzyme Activation, Genotype, Humans, Immunoblotting, Immunohistochemistry, In Situ Hybridization, Male, Mice, Mice, Transgenic, Neovascularization, Pathologic, Oligonucleotide Array Sequence Analysis, Platelet Endothelial Cell Adhesion Molecule-1, Prostate, Prostatic Intraepithelial Neoplasia, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Ribosomal Protein S6 Kinases, 70-kDa, RNA, RNA, Messenger, Transgenes, Urinary Bladder
Abstract

To determine whether Akt activation was sufficient for the transformation of normal prostate epithelial cells, murine prostate restricted Akt kinase activity was generated in transgenic mice (MPAKT mice). Akt expression led to p70S6K activation, prostatic intraepithelial neoplasia (PIN), and bladder obstruction. mRNA expression profiles from MPAKT ventral prostate revealed similarities to human cancer and an angiogenic signature that included three angiogenin family members, one of which was found elevated in the plasma of men with prostate cancer. Thus, the MPAKT model may be useful in studying the role of Akt in prostate epithelial cell transformation and in the discovery of molecular markers relevant to human disease.

DOI10.1073/pnas.1232229100
Alternate JournalProc Natl Acad Sci U S A
PubMed ID12799464
PubMed Central IDPMC164675
Grant ListP01 CA089021 / CA / NCI NIH HHS / United States
P01 CA89021 / CA / NCI NIH HHS / United States
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