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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

PI3K/Akt/JNK/c-Jun Signaling Pathway is a Mediator for Arsenite- Induced Cyclin D1 Expression and Cell Growth in Human Bronchial Epithelial Cells

Author(s): Jin Ding, Beifang Ning, Yi Huang, Dongyun Zhang, Jingxia Li, Chang-Yan Chen and Chuanshu Huang

Volume 9, Issue 4, 2009

Page: [500 - 509] Pages: 10

DOI: 10.2174/156800909788486740

Price: $65


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 (Δp85, 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.

Keywords: PI-3K, Akt, JNK, c-Jun, cyclin D1, arsenite, cell proliferation

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