title: Conditional deletion of the Pten gene in the mouse prostate induces prostatic intraepithelial neoplasms at early ages but a slow progression to prostate tumors.
abstract: 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.
authors: Department of Urology, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Mi Kyung
authors: MK
authors: Kwak
authors: Daniel T
authors: DT
authors: Johnson
authors: Chunfang
authors: C
authors: Zhu
authors: Suk Hyung
authors: SH
authors: Lee
authors: Ding-Wei
authors: DW
authors: Ye
authors: Richard
authors: R
authors: Luong
authors: Zijie
authors: Z
authors: Sun
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000818:Animals; D002369:Castration; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D018703:Founder Effect; D017353:Gene Deletion; D015870:Gene Expression; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: D011944:Receptors, Androgen; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse