Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: The MPAKT model
- Pradip K. Majumder*,†,‡,
- Jen Jen Yeh*,†,‡,
- Daniel J. George*,†,
- Phillip G. Febbo*,†,
- Jennifer Kum*,†,
- Qi Xue*,†,
- Rachel Bikoff*,†,
- Hongfeng Ma*,†,
- Philip W. Kantoff*,†,
- Todd R. Golub§,
- Massimo Loda*,¶, and
- William R. Sellers*,†,∥
- Departments of *Medical Oncology and §Pediatric Oncology, Dana-Farber Cancer Institute, and Departments of †Medicine and ¶Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
-
Communicated by Lewis C. Cantley, Beth Israel Deaconess Medical Center, Boston, MA, April 15, 2003 (received for review January 7, 2003)
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.
Footnotes
-
↵ ∥ To whom correspondence should be addressed at: Dana–Farber Cancer Institute, D720C, 44 Binney Street, Boston, MA 02115. E-mail: William_Sellers{at}dfci.harvard.edu.
-
↵ ‡ P.K.M. and J.J.Y. contributed equally to this work.
-
Abbreviations: PIN, prostate intraepithelial neoplasia; MPAKT, murine prostate restricted Akt kinase transgenic; VP, ventral prostate; PSCA, prostate stem cell antigen; ISH, in situ hybridization; HA, hemagglutinin; myr, myristoylated; LP, lateral prostate; IHC, immunohistochemical analysis; GSK, glycogen synthase kinase.
- Copyright © 2003, The National Academy of Sciences
