Cs. Huang et al., Arsenic-induced NF kappa beta transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells, MOL C BIOCH, 222(1-2), 2001, pp. 29-34
Tumor promoting effects of arsenic are believed to be associated with its t
ransactivation activity on transcription factors, such as AP-1 and NF kappa
B. However, the results from different groups studying the effects of arsen
ic on NF kappaB activation are contradictory in different cell models. Sinc
e 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. Exp
osure of cells to arsenite or arsenate led to NF kappaB transactivation in
mouse epidermal JB6 NF kappaB-luciferase reporter stable transfectants, C14
1 NF kappaB mass(1). This induction of NF kappaB activity by arsenic was do
se- and time-dependent. The transactivation of NF kappaB by arsenic appeare
d to be through activation of Erks and JNKs pathways because increased NF k
appaB activity by arsenic could be dramatically inhibited by either pre-tre
atment of cells with PD98059 or overexpression of dominant negative JNK(1).
That Erks activation is required for arsenic-induced NF kappaB transactiva
tion was further supported by the findings that arsenic-induced NF kappaB t
ransactivation was impaired in JB6 30.7b cells, which were deficient in Erk
s.