Abstract A022: Role of metallothionein in the pathogenesis of prostate cancer

Abstract

Abstract Metallothionein (MT) is a metal binding protein of low molecular weight. It is involved in metal homeostasis, cell differentiation, proliferation, and detoxification of heavy metals. Neoplastic transformation in prostate cancer is attributed to elevated levels of metallothionein. We studied the expression of MT in prostate tissues. Immunohistochemistry (IHC) of 35 prostate cancer patients was performed to evaluate the expression of MT and then correlated with the expression profiles of epithelial TRAIL (Tumor necrosis factor related apoptosis inducing ligand), stromal TRAIL, decoy receptors (DcR1 and DcR2), death receptors (DR4 and DR5), nuclear factor κB (NF-κB), and FLICE inhibitory protein (FLIP). We also correlated expression patterns of these proteins using Pearson correlation with clinical histopathologic factors and determined their influence on overall survival of patients. Elevated levels of MT were observed in cancer tissues as compared to benign controls. Expression levels of epithelial TRAIL, DcR1, DcR2, DR4, DR5, NF-κB, and FLIP were also enhanced in cancer tissue samples. Age at diagnosis was significantly associated with stage (R= -0.467, p=0.046), MT (R= -0.419, p=0.012), DcR1 (R= 0.355, p=0.036) and sTRAIL (R= 0.553, p= 0.001). NF-κB significantly correlated with DR5 expression (R= 0.408, p = 0.015) in tumor tissues. Better survival was observed in patients with MT negative expression (p=0.467). Elevated levels of MT in prostate cancer patients and its positive correlation with FLIP and DcR1 depict its role as an antiapoptotic moiety. Further exploration of the role of MT in prostate cancer pathogenesis could help in establishing MT as a potential therapeutic target. Citation Format: Sobia Hamid, Mariam Anees. Role of metallothionein in the pathogenesis of prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A022.