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Open Access Highly Accessed Research article

Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

Junyi Chen12, Li Jiao1, Chuanliang Xu1, Yongwei Yu3, Zhensheng Zhang1, Zheng Chang1, Zhen Deng1 and Yinghao Sun1*

Author Affiliations

1 Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China

2 Department of Urology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

3 Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China

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BMC Cancer 2012, 12:593  doi:10.1186/1471-2407-12-593

Published: 11 December 2012

Abstract

Background

Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms.

Methods

First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues.

Results

Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion.

Conclusions

Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer.

Keywords:
Prostate cancer; Gamma-synuclein; Androgen receptor; Metastasis