Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Prostate specific G protein coupled receptor is associated with prostate cancer prognosis and affects cancer cell proliferation and invasion

Authors: Wenqing Cao, Faqian Li, Jorge Yao, Jiangzhou Yu

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

There is limited information about the clinical and biological significance of prostate specific G protein coupled receptor (PSGR) in prostate cancer (PCa) initiation and progression. Here, we evaluated the expression of PSGR protein, studied its diagnostic and prognostic value in PCa, and also explored its role in cancer cell growth and invasion.

Methods

The expression of PSGR in paired adjacent normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and PCa were determined by immunohistochemistry on tissue microarrays constructed from 150 radical prostatectomy specimens. The effects of PSGR on PCa cell growth and invasion were investigated using human PCa cell lines.

Results

Membranous and cytoplasmic PSGR staining was observed at luminal epithelial cells of prostate. PSGR protein expression was significantly higher in PIN compared to normal prostate. Interestingly, the expression of PSGR decreased as PIN progressed to PCa. Low PSGR expression in PCa was associated with high Gleason score, and poor overall survival. Activated PSGR increased cancer cell invasive ability, but retarded cell growth. PSGR did not affect mTOR activity, but suppressed P70 S6 kinase activity.

Conclusions

PSGR may participate in PCa progression through affecting cell proliferation and invasion. High expression of PSGR in PIN may implicate its role in early neoplastic transformation of PCa. Low expression of PSGR in PCa may serve as a potential indicator for poor prognosis.
Literature
1.
2.
go back to reference Xu LL, Stackhouse BG, Florence K, Zhang W, Shanmugam N, Sesterhenn IA, et al. PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer. Cancer Res. 2000;60(23):6568–72.PubMed Xu LL, Stackhouse BG, Florence K, Zhang W, Shanmugam N, Sesterhenn IA, et al. PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer. Cancer Res. 2000;60(23):6568–72.PubMed
3.
go back to reference Weng J, Wang J, Cai Y, Stafford LJ, Mitchell D, Ittmann M, et al. Increased expression of prostate-specific G-protein-coupled receptor in human prostate intraepithelial neoplasia and prostate cancers. Int J Cancer. 2005;113(5):811–8.CrossRefPubMed Weng J, Wang J, Cai Y, Stafford LJ, Mitchell D, Ittmann M, et al. Increased expression of prostate-specific G-protein-coupled receptor in human prostate intraepithelial neoplasia and prostate cancers. Int J Cancer. 2005;113(5):811–8.CrossRefPubMed
4.
go back to reference Tang XL, Wang Y, Li DL, Luo J, Liu MY. Orphan G protein-coupled receptors (GPCRs): biological functions and potential drug targets. Acta Pharmacol Sin. 2012;33(3):363–71.CrossRefPubMedPubMedCentral Tang XL, Wang Y, Li DL, Luo J, Liu MY. Orphan G protein-coupled receptors (GPCRs): biological functions and potential drug targets. Acta Pharmacol Sin. 2012;33(3):363–71.CrossRefPubMedPubMedCentral
5.
go back to reference Xu LL, Sun C, Petrovics G, Makarem M, Furusato B, Zhang W, et al. Quantitative expression profile of PSGR in prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(1):56–61.CrossRefPubMed Xu LL, Sun C, Petrovics G, Makarem M, Furusato B, Zhang W, et al. Quantitative expression profile of PSGR in prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(1):56–61.CrossRefPubMed
6.
go back to reference Wang J, Weng J, Cai Y, Penland R, Liu M, Ittmann M. The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase. Prostate. 2006;66(8):847–57.CrossRefPubMed Wang J, Weng J, Cai Y, Penland R, Liu M, Ittmann M. The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase. Prostate. 2006;66(8):847–57.CrossRefPubMed
7.
go back to reference Rigau M, Morote J, Mir MC, Ballesteros C, Ortega I, Sanchez A, et al. PSGR and PCA3 as biomarkers for the detection of prostate cancer in urine. Prostate. 2010;70(16):1760–7.PubMed Rigau M, Morote J, Mir MC, Ballesteros C, Ortega I, Sanchez A, et al. PSGR and PCA3 as biomarkers for the detection of prostate cancer in urine. Prostate. 2010;70(16):1760–7.PubMed
8.
go back to reference Neuhaus EM, Zhang W, Gelis L, Deng Y, Noldus J, Hatt H. Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. J Biol Chem. 2009;284(24):16218–25.CrossRefPubMedPubMedCentral Neuhaus EM, Zhang W, Gelis L, Deng Y, Noldus J, Hatt H. Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. J Biol Chem. 2009;284(24):16218–25.CrossRefPubMedPubMedCentral
9.
go back to reference Spehr J, Gelis L, Osterloh M, Oberland S, Hatt H, Spehr M, et al. G protein-coupled receptor signaling via Src kinase induces endogenous human transient receptor potential vanilloid type 6 (TRPV6) channel activation. J Biol Chem. 2011;286(15):13184–92.CrossRefPubMedPubMedCentral Spehr J, Gelis L, Osterloh M, Oberland S, Hatt H, Spehr M, et al. G protein-coupled receptor signaling via Src kinase induces endogenous human transient receptor potential vanilloid type 6 (TRPV6) channel activation. J Biol Chem. 2011;286(15):13184–92.CrossRefPubMedPubMedCentral
10.
go back to reference Sanz G, Leray I, Dewaele A, Sobilo J, Lerondel S, Bouet S, et al. Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation. PLoS One. 2014;9(1):e85110.CrossRefPubMedPubMedCentral Sanz G, Leray I, Dewaele A, Sobilo J, Lerondel S, Bouet S, et al. Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation. PLoS One. 2014;9(1):e85110.CrossRefPubMedPubMedCentral
11.
go back to reference Ren B, Zakharov V, Yang Q, McMahon L, Yu J, Cao W. MACC1 is related to colorectal cancer initiation and early-stage invasive growth. Am J Clin Pathol. 2013;140(5):701–7.CrossRefPubMed Ren B, Zakharov V, Yang Q, McMahon L, Yu J, Cao W. MACC1 is related to colorectal cancer initiation and early-stage invasive growth. Am J Clin Pathol. 2013;140(5):701–7.CrossRefPubMed
12.
go back to reference Shu C, Cheng H, Wang A, Mansukhani MM, Powell CA, Halmos B, et al. Thymidylate synthase expression and molecular alterations in adenosquamous carcinoma of the lung. Mod Pathol. 2013;26(2):239–46.CrossRefPubMed Shu C, Cheng H, Wang A, Mansukhani MM, Powell CA, Halmos B, et al. Thymidylate synthase expression and molecular alterations in adenosquamous carcinoma of the lung. Mod Pathol. 2013;26(2):239–46.CrossRefPubMed
13.
go back to reference Cao W, Ma Z, Rasenick MM, Yeh S, Yu J. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS One. 2012;7(12):e52838.CrossRefPubMedPubMedCentral Cao W, Ma Z, Rasenick MM, Yeh S, Yu J. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS One. 2012;7(12):e52838.CrossRefPubMedPubMedCentral
14.
go back to reference Yu JZ, Rasenick MM. Real-time visualization of a fluorescent G(alpha)(s): dissociation of the activated G protein from plasma membrane. Mol Pharmacol. 2002;61(2):352–9.CrossRefPubMed Yu JZ, Rasenick MM. Real-time visualization of a fluorescent G(alpha)(s): dissociation of the activated G protein from plasma membrane. Mol Pharmacol. 2002;61(2):352–9.CrossRefPubMed
15.
go back to reference Vojtechova M, Tureckova J, Kucerova D, Sloncova E, Vachtenheim J, Tuhackova Z. Regulation of mTORC1 signaling by Src kinase activity is Akt1-independent in RSV-transformed cells. Neoplasia. 2008;10(2):99–107.CrossRefPubMedPubMedCentral Vojtechova M, Tureckova J, Kucerova D, Sloncova E, Vachtenheim J, Tuhackova Z. Regulation of mTORC1 signaling by Src kinase activity is Akt1-independent in RSV-transformed cells. Neoplasia. 2008;10(2):99–107.CrossRefPubMedPubMedCentral
16.
go back to reference Majumder PK, Sellers WR. Akt-regulated pathways in prostate cancer. Oncogene. 2005;24(50):7465–74.CrossRefPubMed Majumder PK, Sellers WR. Akt-regulated pathways in prostate cancer. Oncogene. 2005;24(50):7465–74.CrossRefPubMed
17.
go back to reference Burgio SL, Fabbri F, Seymour IJ, Zoli W, Amadori D, De Giorgi U. Perspectives on mTOR inhibitors for castration-refractory prostate cancer. Curr Cancer Drug Targets. 2012;12(8):940–9.CrossRefPubMed Burgio SL, Fabbri F, Seymour IJ, Zoli W, Amadori D, De Giorgi U. Perspectives on mTOR inhibitors for castration-refractory prostate cancer. Curr Cancer Drug Targets. 2012;12(8):940–9.CrossRefPubMed
18.
go back to reference Bitting RL, Armstrong AJ. Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer. Endocr Relat Cancer. 2013;20(3):R83–99.CrossRefPubMed Bitting RL, Armstrong AJ. Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer. Endocr Relat Cancer. 2013;20(3):R83–99.CrossRefPubMed
19.
go back to reference Yuan TT, Toy P, McClary JA, Lin RJ, Miyamoto NG, Kretschmer PJ. Cloning and genetic characterization of an evolutionarily conserved human olfactory receptor that is differentially expressed across species. Gene. 2001;278(1–2):41–51.CrossRefPubMed Yuan TT, Toy P, McClary JA, Lin RJ, Miyamoto NG, Kretschmer PJ. Cloning and genetic characterization of an evolutionarily conserved human olfactory receptor that is differentially expressed across species. Gene. 2001;278(1–2):41–51.CrossRefPubMed
20.
go back to reference Xia C, Ma W, Wang F, Hua S, Liu M. Identification of a prostate-specific G-protein coupled receptor in prostate cancer. Oncogene. 2001;20(41):5903–7.CrossRefPubMed Xia C, Ma W, Wang F, Hua S, Liu M. Identification of a prostate-specific G-protein coupled receptor in prostate cancer. Oncogene. 2001;20(41):5903–7.CrossRefPubMed
21.
go back to reference Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227–32.PubMedPubMedCentral Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227–32.PubMedPubMedCentral
22.
go back to reference Rigau M, Ortega I, Mir MC, Ballesteros C, Garcia M, Llaurado M, et al. A three-gene panel on urine increases PSA specificity in the detection of prostate cancer. Prostate. 2011;71(16):1736–45.CrossRefPubMed Rigau M, Ortega I, Mir MC, Ballesteros C, Garcia M, Llaurado M, et al. A three-gene panel on urine increases PSA specificity in the detection of prostate cancer. Prostate. 2011;71(16):1736–45.CrossRefPubMed
24.
go back to reference Berven LA, Willard FS, Crouch MF. Role of the p70(S6K) pathway in regulating the actin cytoskeleton and cell migration. Exp Cell Res. 2004;296(2):183–95.CrossRefPubMed Berven LA, Willard FS, Crouch MF. Role of the p70(S6K) pathway in regulating the actin cytoskeleton and cell migration. Exp Cell Res. 2004;296(2):183–95.CrossRefPubMed
25.
go back to reference Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ, et al. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol Res. 2009;39(2):177–86.CrossRefPubMed Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ, et al. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol Res. 2009;39(2):177–86.CrossRefPubMed
26.
go back to reference Liu L, Li F, Cardelli JA, Martin KA, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene. 2006;25(53):7029–40.CrossRefPubMed Liu L, Li F, Cardelli JA, Martin KA, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene. 2006;25(53):7029–40.CrossRefPubMed
27.
go back to reference Bhola NE, Thomas SM, Freilino M, Joyce S, Sahu A, Maxwell J, et al. Targeting GPCR-mediated p70S6K activity may improve head and neck cancer response to cetuximab. Clin Cancer Res. 2011;17(15):4996–5004.CrossRefPubMedPubMedCentral Bhola NE, Thomas SM, Freilino M, Joyce S, Sahu A, Maxwell J, et al. Targeting GPCR-mediated p70S6K activity may improve head and neck cancer response to cetuximab. Clin Cancer Res. 2011;17(15):4996–5004.CrossRefPubMedPubMedCentral
28.
go back to reference Billington CK, Kong KC, Bhattacharyya R, Wedegaertner PB, Panettieri Jr RA, Chan TO, et al. Cooperative regulation of p70S6 kinase by receptor tyrosine kinases and G protein-coupled receptors augments airway smooth muscle growth. Biochemistry. 2005;44(44):14595–605.CrossRefPubMed Billington CK, Kong KC, Bhattacharyya R, Wedegaertner PB, Panettieri Jr RA, Chan TO, et al. Cooperative regulation of p70S6 kinase by receptor tyrosine kinases and G protein-coupled receptors augments airway smooth muscle growth. Biochemistry. 2005;44(44):14595–605.CrossRefPubMed
Metadata
Title
Prostate specific G protein coupled receptor is associated with prostate cancer prognosis and affects cancer cell proliferation and invasion
Authors
Wenqing Cao
Faqian Li
Jorge Yao
Jiangzhou Yu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1921-6

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine