Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.
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.
Majumder
Pradip K
PK
Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yeh
Jen Jen
JJ
George
Daniel J
DJ
Febbo
Phillip G
PG
Kum
Jennifer
J
Xue
Qi
Q
Bikoff
Rachel
R
Ma
Hongfeng
H
Kantoff
Philip W
PW
Golub
Todd R
TR
Loda
Massimo
M
Sellers
William R
WR
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
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