title: Prostate-specific G-protein-coupled receptor collaborates with loss of PTEN to promote prostate cancer progression.
abstract: 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.
authors.affiliation: Center for Cancer and Stem Cell Biology, Department of Cellular and Molecular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Center for Cancer and Stem Cell Biology, Department of Cellular and Molecular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Siwko
authors.affiliation: Center for Cancer and Stem Cell Biology, Department of Cellular and Molecular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Center for Cancer and Stem Cell Biology, Department of Cellular and Molecular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D018035:Receptors, Odorant / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D009363:Neoplasm Proteins; C417566:OR51E2 protein, human; D018035:Receptors, Odorant; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human