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

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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.