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

Oncogene volume 35, pages 1153–1162 (2016)Cite this article

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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-PtenΔ/Δ) combining prostate-specific loss of Pten with probasin promoter-driven PSGR overexpression. By 12 months PSGR-PtenΔ/Δ mice developed invasive prostate tumors featuring Akt activation and extensive inflammatory cell infiltration. PSGR-PtenΔ/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.

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Acknowledgements

We thank Dr Michael Ittmann (Baylor College of Medicine) for his insights and suggestions. We thank Dr Fen Wang (Texas A&M Health Science Center) for the gift of the PTENfl/fl Cre mice and for valuable discussions and suggestions, and Dr Dekai Zhang (Texas A&M Health Science Center) for the gift of the RAW264.7 cells. This work was partially supported by grants from the State Key Development Programs of China (2012CB910400), DOD Prostate Cancer Research Program (PCRP, W81XWH-10-1-0612, W81XWH-10-10147) and NIH (5R01CA134731). This work was partially supported by grants from the State Key Development Programs of China (2012CB910400), DOD Prostate Cancer Research Program (PCRP, W81XWH-10-1-0612, W81XWH-10-10147) and NIH (5R01CA134731).

Author Contributions

M Rodriguez: Experimental design, data collection, data analysis, manuscript writing; S Siwko: Experimental design, data analysis, manuscript writing; L Zeng, J Li and Z Yi: Data collection and analysis; M Liu: Overall direction, experimental design and analysis, final approval of completed manuscript.

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Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA

    M Rodriguez, S Siwko, L Zeng & M Liu

  2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

    J Li, Z Yi & M Liu

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  1. M Rodriguez
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Correspondence to M Liu.

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Rodriguez, M., Siwko, S., Zeng, L. et al. Prostate-specific G-protein-coupled receptor collaborates with loss of PTEN to promote prostate cancer progression. Oncogene 35, 1153–1162 (2016). https://doi.org/10.1038/onc.2015.170

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