TY - JOUR
T1 - Arsenic-induced NFκB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells
AU - Huang, C.
AU - Li, J.
AU - Ding, M.
AU - Wang, L.
AU - Shi, X.
AU - Castranova, V.
AU - Vallyathan, V.
AU - Ju, G.
AU - Costa, M.
PY - 2001
Y1 - 2001
N2 - Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFκB. However, the results from different groups studying the effects of arsenic on NFκB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFκB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFκB transactivation in mouse epidermal JB6 NFκB-luciferase reporter stable transfectants, C141 NFκB mass. This induction of NFκB activity by arsenic was dose- and time-dependent. The transactivation of NFκB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFκB 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 NFκB transactivation was further supported by the findings that arsenic-induced NFκB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.
AB - Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFκB. However, the results from different groups studying the effects of arsenic on NFκB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFκB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFκB transactivation in mouse epidermal JB6 NFκB-luciferase reporter stable transfectants, C141 NFκB mass. This induction of NFκB activity by arsenic was dose- and time-dependent. The transactivation of NFκB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFκB 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 NFκB transactivation was further supported by the findings that arsenic-induced NFκB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.
KW - Arsenic
KW - MAP kinase
KW - NFκB
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U2 - 10.1023/A:1017974131948
DO - 10.1023/A:1017974131948
M3 - Article
C2 - 11678607
AN - SCOPUS:0034741121
SN - 0300-8177
VL - 222
SP - 29
EP - 34
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -