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.
Stewart
Grant D
GD
Tissue Injury and Repair Group, University of Edinburgh, UK. grantstewart@rcsed.ac.uk
Lowrie
Alastair G
AG
Riddick
Antony C P
AC
Fearon
Kenneth C H
KC
Habib
Fouad K
FK
Ross
James A
JA
D016923:Cell Death / Q000235:genetics / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology; D010455:Peptides; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014162:Transfection
D004273:DNA, Neoplasm; D009419:Nerve Tissue Proteins; D010455:Peptides; D012334:RNA, Neoplasm; C442243:dermcidin