Abstract B24: Role of Dermcidin in growth and survival of melanoma tumor cells

Abstract

Dermcidin (DCD) is a candidate oncogene localized at 12q13.1 which is normally expressed in the skin sweat gland and brain and overexpressed in various tumor cells. We have established the role of DCD in melanoma growth and survival by silencing DCD via shRNA expression in human melanoma G361 cell line. Biologic and biochemical assays showed that DCD gene knockdown decreased significantly melanoma cell growth in culture and tumor formation in NUDE mice. A DNA microarray-based study identified a total of 162 upregulated and 212 downregulated genes, in a G-361 control clone (pLKO) and clones expressing shRNA to DCD mRNA (IBC-I). We found, notably, genes involved in the nucleosome organization and signaling pathway to APRIL/BAFF receptor. Additionally, we examined DCD expression by immunohistochemistry in TMA (tissue microarray) of 101 patients and found that DCD-negative tumor had a 65.54% survival rate and DCD-positive tumor 43.33% survival rate in 5 years. We found an association with BRAF V600E and ERBB4 mutation in DCD-positive tumor with most frequent E43K mutation. Finally, we have screened clones resistant to Vemurafenib after long-term treatment in vitro and in xenografts in nude mice. Overall, these studies provide further support for DCD as oncogene to melanomas. Financial support: FAPESP, CNPq and CAPES. Citation Format: Jennifer N. Montoya, Marcela N. Perez-Sosa, Beatriz A. Sangiuliano, Jose E. Belizario. Role of Dermcidin in growth and survival of melanoma tumor cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B24.