Open AccessConditional Deletion of the Pten Gene in the Mouse Prostate Induces Prostatic Intraepithelial Neoplasms at Early Ages but a Slow Progression to Prostate Tumors
Author(s) -
Mi Kyung Kwak,
Daniel T. Johnson,
Chunfang Zhu,
Suk Hyung Lee,
Ding Wei Ye,
Richard Luong,
Zijie Sun
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0053476
Subject(s) - pten , prostate cancer , prostate , cancer research , conditional gene knockout , biology , tumor suppressor gene , lncap , intraepithelial neoplasia , tensin , knockout mouse , cancer , pi3k/akt/mtor pathway , carcinogenesis , gene , phenotype , signal transduction , genetics
The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 ( odd skipped related 1 )- Cre mice, we generated a novel conditional Pten knockout mouse strain, Pten LoxP :Osr1-Cre . Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of Pten LoxP/LoxP :Osr1-Cre mice as early as 2 weeks of age. Intriguingly, Pten LoxP/LoxP : Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. Pten LoxP/+ : Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of Pten LoxP/LoxP : Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated Pten LoxP/LoxP :Osr1-Cre . This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate.