Involvement of Erks activation in cadmium-induced AP-1 transactivation in vitro and in vivo.
Huang-C; Zhang-Q; Li-J; Shi-X; Castranova-V; Ju-G; Costa-M; Dong-Z
Mol Cell Biochem 2001 Jun; 222(1-2):141-147
Cadmium is a potent and effective carcinogen in rodents and has recently been accepted by IARC (International Agency for Research on Cancer) as a category I carcinogen. Cadmium-induced up-regulation of intracellular signaling pathways leading to increased mitogenesis is thought to be a major mechanism for the carcinogenic activity following chronic cadmium exposure. In the present study, we found that exposure of cells to cadmium induced significant activation of AP-1 and all three members of the MAP kinase family in mouse epidermal JB6 cells. The induction of AP-1 activity by cadmium appears to involve activation of Erks, since the induction of AP-1 activity by cadmium was blocked by pretreatment of cells with PD98058. Interestingly, the induction of AP-1 by cadmium was greatly enhanced by the chemical tumor promoter, TPA and the growth factor EGF, but not by ultraviolet C radiation. In vivo studies demonstrated that cadmium could also induce transactivation of AP-1 in AP-1-luciferase report transgenic mice. Considering the role of AP-1 activation in tumor promotion, the results presented in this study provide a possible molecular mechanism for cadmium-induced carcinogenesis.
Cadmium-compounds; In-vitro-studies; In-vivo-studies; Carcinogens; Carcinogenesis; Carcinogenicity; Exposure-levels; Exposure-assessment; Growth-factors
Nelson Institute of Environmental Medicine, New York University School of Medicine, NY 10016
Molecular and Cellular Biochemistry