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Publication Detail

Title: PI3K/Akt/JNK/c-Jun signaling pathway is a mediator for arsenite-induced cyclin D1 expression and cell growth in human bronchial epithelial cells.

Authors: Ding, Jin; Ning, Beifang; Huang, Yi; Zhang, Dongyun; Li, Jingxia; Chen, Chang-Yan; Huang, Chuanshu

Published In Curr Cancer Drug Targets, (2009 Jun)

Abstract: Arsenite exposure is associated with an increased risk of human lung cancer. However, the molecular mechanisms underlying the arsenite-induced human lung carcinogenesis remain elusive. In this study, we demonstrated that arsenite upregulates cyclin D1 expression/activity to promote the growth of human bronchial epithelial Beas-2B cells. In this process, the JNKs (c-Jun N-terminal kinases)/c-Jun cascade is elicited. The inhibition of JNKs or c-Jun by chemical or genetic inhibitors blocks the cyclin D1 induction mediated by arsenite. Furthermore, using a loss of function mutant of p85 (Deltap85, a subunit of PI3K) or dominant-negative Akt (DN-Akt), we showed that PI3K and Akt act as the upstream regulators of JNKs and c-Jun in arsenite-mediated growth promotion. Overall, our data suggest a pathway of PI-3K/Akt/JNK/c-Jun/cylin D1 signaling in response to arsenite in human bronchial epithelial cells.

PubMed ID: 19519318 Exiting the NIEHS site

MeSH Terms: Arsenites/toxicity*; Bronchi/drug effects; Bronchi/metabolism; Cell Proliferation/drug effects; Cells, Cultured; Cyclin D1/metabolism*; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; NF-kappa B/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Proto-Oncogene Proteins c-jun/metabolism; Respiratory Mucosa/drug effects*; Respiratory Mucosa/metabolism; Signal Transduction/drug effects*; Up-Regulation

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