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

Abstract

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.

• Authors: Grant D Stewart, Alastair G Lowrie, Antony C P Riddick, Kenneth C H Fearon, Fouad K Habib, James A Ross
• Journal: The Prostate (Prostate) Vol. 67 Issue 12 Pg. 1308-17 (Sep 01 2007) ISSN: 0270-4137 [Print] United States
• PMID: 17626247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Nerve Tissue Proteins
• Peptides
• RNA, Neoplasm
• dermcidin

Topics

• Cell Death (genetics, physiology)
• Cell Hypoxia (physiology)
• Cell Line, Tumor
• Cloning, Molecular
• DNA, Neoplasm (chemistry, genetics)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Male
• Mutagenesis, Site-Directed
• Nerve Tissue Proteins (biosynthesis, genetics)
• Oxidative Stress (physiology)
• Peptides
• Prostatic Neoplasms (genetics, metabolism)
• RNA, Neoplasm (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Statistics, Nonparametric
• Transfection