Arsenic-induced NFκβ transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells
Arsenic-induced NFκβ transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells
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DOI：
10.1023/a:1017974131948
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发表时间：
2001-06-01
影响因子：
4.3
通讯作者：
Costa, M
中科院分区：
文献类型：
--
作者：
Huang, CS;Li, JX;Costa, M
砷的促肿瘤作用被认为与其对转录因子如AP-1和NF κ B的反式激活活性有关。然而，来自不同研究小组的砷对NF κ B活化的影响的结果在不同的细胞模型中是矛盾的。由于砷是一种强烈的皮肤致癌物，我们研究了砷在小鼠皮肤表皮细胞系JB 6细胞中对NF κ B的激活。在小鼠表皮JB 6 NF kappaB-荧光素酶报告基因稳定转染子C141 NF kappaB mass中，细胞暴露于亚砷酸盐或砷酸盐导致NF kappaB反式激活（1）。砷对NF-κ B活性的诱导具有剂量和时间依赖性。砷对NF kappaB的反式激活似乎是通过激活Erks和JNK途径，因为砷增加的NF kappaB活性可以通过用PD 98059预处理细胞或过表达显性阴性JNK来显著抑制（1）。砷诱导的NF kappaB反式激活需要Erks激活，这一发现进一步支持砷诱导的NF kappaB反式激活在缺乏Erks的JB 6 30.7b细胞中受损。
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.