Inhibition of N-myc downstream-regulated gene 2 in prostatic carcinoma.

摘要

To study the expression of N-myc Downstream Regulated Gene-2 (NDRG2) in prostatic carcinoma (PCA) tissue and in different PCA cell lines, and to investigate its clinical and pathological implications, 144 PCA and benign prostatic hyperplasia (BPH) tissue sections were analyzed retrospectively with immunohistochemistry (S-P method). The expression levels of NDRG2 and c-Myc in prostate cell lines were detected through Western blot. The effects of adenovirus-mediated NDRG2 on PC3 cells and PC3 nude mouse xenografts was observed through cell growth curves, tumor growth curves, flow cytometry (FCM), transmission electron microscopy (TEM) and TUNEL staining. The NDRG2 gene was highly expressed in BPH tissues, but not in carcinomatous ones (chi(2)=25.98, p < 0.001). Furthermore, positive expression of NDRG2 was negatively correlated with the Gleason score (r = -0.445, p< 0.001) and the c-myc level (r = -0.311, p < 0.001). However, positive expression of NDRG2 was not correlated with pTNM tumor stages or the serum concentration of prostate-specific antigen (PSA) (p > 0.05). The expression of the NDRG2 genes was low in the three PCA cell lines. PC3 cells infected by pAD-cmv-NDRG2 showed inhibition of proliferation both in vitro and vivo. To sum up, NDRG2 may be involved in the carcinogenesis and progression of PCA. Moreover, adenovirus-mediated NDRG2 can suppress the proliferation of PC3 cells significantly both in vitro and in vivo. These results indicate that NDRG2 may become a new target gene for PCA diagnosis and therapy.