Functional and Expression Analyses of Endoplasmic Reticulum Stress Response Genes in Prostate Cancer

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NDRG1, which was originally identified as a N-myc downstream-regulated gene, is now considered to play a role in cell growth, differentiation, carcinogenesis as well as cellular stress responses. We have reported that the expressions of ER stress responsive genes including NDRG1 were regulated by androgen in a time and dose dependent manner in LNCaP, and that the RNA expression of NDRG1 was decreased in prostate cancer (CaP) compared to normal prostate. In this study we investigated the effects of NDRG1 on the androgen sensitivity in LNCaP cells. LNCaP clones stably expressing NDRG1 (LNCaP-NDRG1) were obtained. Parental LNCaP and LNCaP-NDRG1 cells were cultured without androgen, and then stimulated with synthetic androgen R1881 at 0.01 nM to 100 nM concentrations. Cell proliferation was examined by MTT assay. Proliferation of LNCaP was bi-phasically regulated by androgen, with the optimum of 0.1nM R1881 stimulation, as reported. The optimal condition for LNCaP-NDRG1 cells was shifted t … More o higher R1881 concentration than parental LNCaP cells, suggesting an effect of NDRG1 on the androgen sensitivity in LNCaP cells. Then, we analyzed the protein expressions of NDRG1 and androgen receptor (AR) in radical prostatectomy specimens to investigate the impact of NDRG1 expression on clinical or pathological features of CaP patients. Tissue microarray of 260 spots from 70 CaP patients was immunohistochemically analyzed. Expressions of NDRG1 and AR in CaP tissues were compared with those in normal tissues and correlation among NDRG1, AR expressions and clinical or pathological parameters were analyzed. NDRG1 was expressed both in normal and CaP epithelial cells, but not in stromal cells. When compared with normal tissues, NDRG1 protein expression was decreased in 47% of CaP tissues, consistent with RNA expression data. AR expression was positively correlated with NDRG1 expression, suggesting androgen-regulated expression of NDRG1 in CaP tissues. NDRG1 expression was not correlated with other clinical or pathological features, including Gleason score, and PSA failure after radical prostatectomy. Less