A Novel Controlled PTEN-Knockout Mouse Model for Prostate Cancer Study

作者：Sen Liu, Bing Zhang, Brian G. Rowan, S. Michal Jazwinski, Asim B. Abdel‐Mageed, Chad Steele, Alun R. Wang, Oliver Sartor, Tianhua Niu, Qiuyang Zhang · 发表于：Frontiers in Molecular Biosciences · 年份：2021 · DOI：10.3389/fmolb.2021.696537 · 被引用次数：15 · 研究领域：Prostate Cancer Treatment and Research、Molecular Biology Techniques and Applications、Viral Infectious Diseases and Gene Expression in Insects

Prostate cancer (PCa) is associated with advanced age, but how age contributes to prostate carcinogenesis remains unknown. The prostate-specific Pten conditional knockout mouse model closely imitates human PCa initiation and progression. To better understand how age impacts PCa in an experimental model, we have generated a spatially and temporally controlled Pten-null PCa murine model at different ages (aged vs. non-aged) of adult mice. Here, we present a protocol to inject the Cre-expressing adenovirus with luciferin tag, intraductally, into the prostate anterior lobes of Pten-floxed mice; Pten-loss will be triggered post-Cre expression at different ages. In vivo imaging of luciferin signal following viral infection confirmed successful delivery of the virus and Cre activity. Immunohistochemical staining confirmed prostate epithelial-specific expression of Cre recombinase and the loss of Pten and activation of P-Akt, P-S6, and P-4E-BP1. The Cre-expression, Pten ablation, and activated PI3K/AKT/mTOR pathways were limited to the prostate epithelium. All mice developed prostatic epithelial hyperplasia within 4 weeks after Pten ablation and prostatic intraepithelial neoplasia (PIN) within 8 weeks post-Pten ablation. Some PINs had progressed to invasive adenocarcinoma at 8–16 weeks post-Pten ablation. Aged mice exhibited significantly accelerated PI3K/AKT/mTOR signaling and increased PCa onset and progression compared to young mice. The viral infection success rate is ∼80%. This ...