Role of Dermcidin in Tumorigenesis of Malignant Melanoma

Abstract

Question: Dermcidin (DCD) gene is localized at 12q13.1 and encode a precursor protein secreted by dark cells of eccrine sweat glands which is proteolytic processed and transported via sweat to the epidermal surface where it acts as peptide antibiotic and/or growth and cell survival factor. This study aims to investigate oncogenic path-ways modulated by DCD in malignant melanomas. Methods: We generated cell clones expressing DCD shRNA and established in vitro and in vivo models to investigate the role of DCD in proliferation and cell survival and tumorigenicity of human melanoma cell line G-361. The global gene expression profiling was done using Affymetrix GeneChip Human 1.0 ST array and the net-work analysis using MetaCore software. The quantitative RT-PCR analysis was performed using SYBR Green kit on MX3005 qPCR system and gene expression analysis was done using REST software. The presence of DCD was assessed using specific antibody in tissue array (TMA) containing primary and metastatic human malignant melanoma samples. Results: Biological and biochemical assays showed that the “knock-down” in the expression of DCD in malignant melanoma G-361 via RNA interference (RNAi) decreased significantly the in vitro growth in cell culture and tumor growth in nude mice. A total of 213 genes were differentially and repeatedly expressed (>3-fold change and p<0.005). Several molecular pathways and genes were differentially up and down regulated by DCD knockdown including genes involved in nucleosome and chromatin organization. DCD was expressed in primary and metastatic, melanocytic and amelanocytic melanomas at moderate and high levels. Conclusion: Overall our studies suggest that DCD functions as tumor growth and cell survival factor in subset of malignant melanomas.