Expression of STAT3 and Bcl-6 oncoprotein in sodium arsenite-treated SV-40 immortalized human uroepithelial cells

Abstract

Arsenic is widely distributed in the environment, and it is a proven toxic and carcinogenic agent. On the southwest coast of Taiwan, an endemic occurrence of chronic arsenical poisoning due to a high concentration of arsenic in artesian-well water has been reported. However, the mechanisms of its carcinogenic action are still unclear. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is an essential cascade for mediating normal functions of different cytokines in the development of the hematopoietic and immune systems. In this study, the substantial morphological changes observed in SV-40 immortalized human uroepithelial cells (SV-HUC-1) after treatment of various concentrations of arsenite were examined, and the expression of Bcl-6, Jak-2 and p-STAT3 (Tyr 705) were evaluated by immunocytochemistry and Western blotting. Our results showed that the expression of Bcl-6 increased dose-dependently in arsenite-treated urothelial cells. Sodium arsenite treatment reduced Jak-2 protein expression in a dose-dependent manner. However, treatment of SV-HUC-1 cells with arsenite at concentration ranges from 2 and 4 μM for 48 h dramatically increased p-STAT3 (Tyr 705), but the levels decreased at 8–40 μM of arsenite. Our data suggest that arsenic-mediated inactivation of the JAK-STAT signaling pathway might be caused by Bcl-6 interaction with JAK tyrosine kinase or STAT. In conclusion, our findings indicate that arsenic inhibits JAK tyrosine kinase protein expression and suggest the interference in the JAK-STAT pathway might be through Bcl-6 playing an important role in arsenic-associated carcinogenesis.