NDRG3 is an androgen regulated and prostate enriched gene that promotes in vitro and in vivo prostate cancer cell growth

Authors

  • Weiqun Wang,

    1. Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China
    2. Department of Pathophysiology, Norman Bethune Medical College, Jilin University, Changchun, Jilin, China
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    • Weiqun Wang and Yuhua Li contributed equally to this work.

  • Yuhua Li,

    1. Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China
    2. Department of Pathophysiology, Norman Bethune Medical College, Jilin University, Changchun, Jilin, China
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    • Weiqun Wang and Yuhua Li contributed equally to this work.

  • Yang Li,

    1. Department of Pathophysiology, Norman Bethune Medical College, Jilin University, Changchun, Jilin, China
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  • Aizhen Hong,

    1. Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China
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  • Jian Wang,

    1. Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China
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  • Biaoyang Lin,

    Corresponding author
    1. Division of Systems Biology, Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, Zhejiang, China
    2. Neuroscience Institute, Swedish Medical Center, Seattle, WA
    3. Department of Urology, University of Washington, Seattle, WA
    • Division of Systems Biology, Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, China, 310029
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    • Fax: +86 (0571)-86971851 or (206) 320-3166

  • Runsheng Li

    Corresponding author
    1. Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China
    • Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China, 200030
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    • Fax: +86 (021) 6443-7446


Abstract

NDRG3 belongs to the N-myc down-regulated gene (NDRG) family that contains 4 paralogs: NDRG1, -2, -3 and -4. The function of NDRG3 and its relationship to cancer has not been studied. We herein report our examination of the expression and biological roles of NDRG3 in prostate cancers. We showed that NDRG3 expression is enriched in testis and prostate using gene expression data derived from massively parallel signature sequencing from 33 different human organs. We further showed that NDRG3 is expressed in both epithelial prostate cancer cells and prostatic stromal cells at both mRNA and proteins levels. We demonstrated that NDRG1 is significantly up-regulated by androgen in LNCaP cells. Over-expression of NDRG3 in stably transfected PC-3 cells increased their growth rates and migration capabilities when compared to parental or mock empty vector transfected PC-3 cells. In addition, we found that overexpresson of NDRG3 promoted the growth of xenograft tumors in nude mice. Finally, we found that NDRG3 expression was detected in 58.6% (41/70) of prostate cancer specimens compared to 13.2% (5/38) of benign prostatic hyperplasia specimens by immunohistochemistry. We showed by microarray and by RT-PCR that NDRG3 overexpression up-regulates the expression of many angiogenic chemokines including CXCL1 (chemokine ligand 1), CXCL3 (chemokine ligand 3) and CXCL5 (chemokine ligand 5), which may increase angiogenesis of tumors. Taken together, these results demonstrate that NDRG3 is a tumor promoter, the overexpression of which may contribute to the malignant phenotype of tumors. © 2008 Wiley-Liss, Inc.

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