title: Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Majumder
authors.forename: Jen Jen
authors.initials: JJ
authors.lastname: Yeh
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Febbo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kum
authors.forename: Qi
authors.initials: Q
authors.lastname: Xue
authors.forename: Rachel
authors.initials: R
authors.lastname: Bikoff
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Ma
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011467:Prostate / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology* / Q000209:etiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D019076:Transgenes; D001743:Urinary Bladder / Q000473:pathology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012313:RNA; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa