Discussion Earlier immunolabeling studies with selleck screening library polyclonal antibodies had revealed that the RPS2 antigen was over-expressed in 100% of prostate cancer luminal epithelial cells (n = 20 prostates examined). In contrast, the AP26113 manufacturer protein was not expressed in NPTX-1532, benign prostate hyperplasia (BPH), seminal vesicle (SV) or in skeletal or smooth muscle tissues from the same prostates with (or without) cancer foci [1]. Likewise, RPS2 (aka: PCADM-1) was not expressed by primary prostate tissue fibroblast

cultures, WI38 human fibroblasts, human peripheral blood lymphocytes or human hepatocyte cultures [1]. In this paper, we have examined whether the PCADM-1 gene/protein is normally over expressed in malignant prostate cancer. Western blots indicated benign prostate did not express the protein, whereas malignant prostate cancer expressed PCADM-1 and the amount of RPS2 expressed increased with the tumor grade. We have, therefore, focused on studies designed to test whether RPS2 over expression in prostate cancer cell lines is essential for cell survival. To our surprise, CH5424802 ic50 we found in ‘anti-sense’ knock-out experiments with a DNAZYM-1P which targeted the RPS2 mRNA, that gene expression was essential for cell survival, but only in cells which over expressed the RPS2 protein

(i.e. in PC-3 ML, LNCaP, CPTX-1532 and pBABE-IBC-10a-c-myc cells). In comparison, prostate cell lines expressing very little RPS2 (i.e. BPH-1, NPTX-1532 or IBC-10a cells) were not affected by the DNAZYM-1P treatment

even at high concentrations for prolonged intervals. That is, only the PC-3ML and pBABE- IBC-10a-c-myc cells which expressed elevated RPS2 underwent apoptosis and failed not to grow in response to DNAZYM-1P. NPTX-1532 or IBC-10a cells which failed to express detectable RPS2 did not undergo apoptosis. Likewise, DNAZYM-1P treatment of localized or metastatic tumors in SCID mice, completely eradicated the tumors, but did not inflict noticeable harm to normal mouse cells. We interpret this to mean that the over-expression of RPS2 might promote ribosomal biogenesis and growth of tumor cells and that the tumor cells acquire a dependence on RPS2 for survival. Thus, ‘knock-out’ of RPS2 results in a ‘shut-down’ of ribosomal biogenesis and a cascade of apoptotic events leading to inhibition of cell growth and apoptosis. Again, a similar response was not observed in normal cells since the temporary ‘knock-down’ of RPS2 mRNA had little impact on overall cell homeostasis. Perhaps more importantly, we found that DNAZYM-1P treatment of tumor bearing mice was a highly effective therapeutic approach to eradicating tumors and dramatically improving disease free mouse survival rates. We showed that the DNAZYM-1P eliminated PC-3ML tumors in mice (> 90%) and that treatment resulted in a significant increase in disease free mouse survival rates (> 80–100%) after discontinuation of the treatment for ~4 mos.