Prostate-specific G-protein-coupled receptor collaborates with loss of PTEN to promote prostate cancer progression

Among frequent events in prostate cancer are loss of the tumor-suppressor phosphatase and tensin homologue (PTEN) and overexpression of prostate-specific G-protein-coupled receptor (PSGR), but the potential tumorigenic synergy between these lesions is unknown. Here, we report a new mouse model (PSGR...

Full description

Saved in:
Bibliographic Details
Published in:Oncogene 2016-03, Vol.35 (9), p.1153-1162
Main Authors: Rodriguez, M, Siwko, S, Zeng, L, Li, J, Yi, Z, Liu, M
Format: Article
Language:English
Subjects:
AKT protein
Analysis
Androgen receptors
Animals
Cadherins - biosynthesis
Cadherins - genetics
Carcinogenesis - genetics
Care and treatment
Cell activation
Cell adhesion & migration
Cell Movement - genetics
Cell Proliferation - genetics
Complications and side effects
Development and progression
E-cadherin
G protein-coupled receptors
G proteins
Gene Expression Regulation, Neoplastic
Humans
Inflammation
Influence
Invasiveness
Male
Metastases
Mice
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Neurons
Phosphatases
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Proteins
PTEN Phosphohydrolase - genetics
PTEN protein
Receptors, Odorant - biosynthesis
Receptors, Odorant - genetics
Tensin
Tumors
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Among frequent events in prostate cancer are loss of the tumor-suppressor phosphatase and tensin homologue (PTEN) and overexpression of prostate-specific G-protein-coupled receptor (PSGR), but the potential tumorigenic synergy between these lesions is unknown. Here, we report a new mouse model (PSGR-Pten(Δ/Δ)) combining prostate-specific loss of Pten with probasin promoter-driven PSGR overexpression. By 12 months PSGR-Pten(Δ/Δ) mice developed invasive prostate tumors featuring Akt activation and extensive inflammatory cell infiltration. PSGR-Pten(Δ/Δ) tumors exhibited E-cadherin loss and increased stromal androgen receptor (AR) expression. PSGR overexpression increased LNCaP proliferation, whereas PSGR short hairpin RNA knockdown inhibited proliferation and migration. In conclusion, we demonstrate that PSGR overexpression synergizes with loss of PTEN to accelerate prostate cancer development, and present a novel bigenic mouse model that mimics the human condition, where both PSGR overexpression and loss of PTEN occur concordantly in the majority of advanced prostate cancers, yielding an environment more relevant to studying human prostate cancer.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2015.170