Dermcidin expression confers a survival advantage in prostate cancer cells subjected to oxidative stress or hypoxia

BACKGROUND Dermcidin (DCD) is a candidate survival gene in breast cancer. DCD gene expression has been identified in prostate cancer cell lines and primary prostate cancer tissue. The DCD protein is composed of proteolysis‐inducing factor‐core peptide (PIF‐CP) and the skin antimicrobial DCD‐1. The aim of this work was to: (i) establish if the DCD gene confers resistance of prostate cancer cells to hypoxia and oxidative stress; (ii) identify the component of the gene transcript responsible for this effect. METHODS Site‐directed mutagenesis was used to create mutant DCD vectors. PC‐3M prostate cancer cells were stably transfected with pcDNA3.1+ vectors encoding the entire DCD cDNA, mutant DCD vectors, or a control empty vector. Oxidative stress was produced using menadione, glucose oxidase, or hydrogen peroxide. Cell hypoxia was induced by incubation at 0.2% oxygen. RESULTS Comparison of cell growth showed a 54.5% relative‐proliferative advantage for the DCD‐transfected PC‐3M cells compared with sham‐transfected cells after 8 days of cell growth (P = 0.03). Overexpression of DCD provided upto 36% absolute survival advantage over sham‐transfected cells following induction of oxidative stress or hypoxia (P = 0.004). On exposure to hypoxia or oxidative stress PC‐3M cells overexpressing the entire DCD gene had upto 42% survival advantage over those transfectants lacking the PIF‐CP sequence (P = 0.004). CONCLUSIONS DCD and PIF‐CP are proliferation and survival factors in prostate cancer cells subjected to stressors found in the prostate cancer microenvironment. Thus, DCD and specifically PIF‐CP are potential targets for the treatment of prostate cancer. Prostate 67: 1308–1317, 2007. © 2007 Wiley‐Liss, Inc.