Proteins in the ERK pathway are affected by arsenic-treated cells

Abstract

Epidemiological studies have demonstrated that an elevated risk of bladder cancer and amount of arsenic exposure are positively correlated in residential southwestern Taiwan, where certain areas are contaminated with arsenic; the so-called black-foot disease (BFD) area. Some studies have suggested that ERK plays an important role in arsenic carcinogenesis. However, the mechanism of arsenic-induced bladder carcinogenesis is still unclear. In this study, we performed proteomic analysis to investigate the effect of arsenic on protein profile and evaluated the role of the ERK-signaling pathway in human uroepithelial cells. Our results showed that four arsenic-induced proteins were up-regulated and thirteen arsenic-induced proteins were down-regulated in human uroepithelial cells. Five identified differential expression proteins (SLC25A12, PSME3, vinculin, QR and STIP1) were confirmed by western blotting and immunohistochemistry in arsenic-treated human uroepithelial cells and urothelial carcinomas from non-BFD and BFD areas. In addition, U0126, a highly selective inhibitor of both MEK1 and MEK2 in the ERK pathway inhibited the effects of arsenic on these significant protein expressions in an in vitro study. These results suggest that arsenic regulates these protein expressions possibly through activation of the ERK signaling pathway, and that SLC25A12, PSME3, vinculin, QR and STIP1 might play a role in arsenic-induced bladder carcinogenesis.