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Hexavalent chromium-induced COX-2 overexpression.

Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen following inhalation exposure, but the molecular mechanisms by which Cr(VI) causes cancer are nor well understood. Zuo et al. (p. 547) studied the effects of exposure to Cr(V1) on the induction of cyclooxygenase-2 (COX-2) expression in cultured cells. The authors used the luciferase reporter assay and Western blot analysis to determine COX-2 induction by Cr(VI); dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches were used to elucidate the signaling pathway leading to COX-2 induction. The authors report that exposure to Cr(VI) induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration-and time-dependent mariner. Deletion of IKK[beta] (an upstream kinase responsible for NFKB activation) or overexpression of TAM67 (a dominant negative mutant of clun) dramatically inhibited COX-2 induction due to Cr(VI), suggesting that both NFKB and c-Jun/ AP-1 pathways are required for Cr(VI)-induced COX-2 expression. The authors conclude that p65 and c-Jun were major components involved in NFKB and AP-1 activation, respectively, and that there was cross-talk between NFKB and c-Jun/ AP-1 pathways in response to Cr(VI) exposure. This study may provide insight into the molecular mechanisms linking Cr(VI) to lung inflammation and carcinogenesis.

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Title Annotation:Research; cyclooxygenase-2
Publication:Environmental Health Perspectives
Article Type:Brief article
Geographic Code:1USA
Date:Apr 1, 2012
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