Arsenic-induced NFκβ transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NF kappaB. However, the results from different groups studying the effects of arsenic on NF kappaB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NF kappaB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NF kappaB transactivation in mouse epidermal JB6 NF kappaB-luciferase reporter stable transfectants, C141 NF kappaB mass(1). This induction of NF kappaB activity by arsenic was dose- and time-dependent. The transactivation of NF kappaB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NF kappaB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK(1). That Erks activation is required for arsenic-induced NF kappaB transactivation was further supported by the findings that arsenic-induced NF kappaB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.