Arsenic-induced NFkB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells.
Huang-C; Li-J; Ding-M; Wang-L; Shi-X; Castranova-V; Vallyathan-V; Ju-G; Costa-M
Mol Cell Biochem 2001 Jun; 222(1-2):29-34
Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFkappaB. However, the results from different groups studying the effects of arsenic on NFkappaB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFkappaB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFkappaB transactivation in mouse epidermal JB6 NFkappaB-luciferase reporter stable transfectants, C141 NFkappaB mass1. This induction of NFkappaB activity by arsenic was dose- and time-dependent. The transactivation of NFkappaB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFkappaB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK1. That Erks activation is required for arsenic-induced NFkappaB transactivation was further supported by the findings that arsenic-induced NFkappaB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.
Arsenic-compounds; Laboratory-animals; Animals; Animal-studies; Tumors; Models; Cell-cultures; Skin-disorders; Carcinogens; Exposure-levels; Exposure-assessment
Nelson Institute of Environmental Medicine, New York University School of Medicine, NY 10016
Molecular and Cellular Biochemistry