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, Chuanshu Huang.

Journal Name: Current Cancer Drug Targets

Volume 9 , Issue 4 , 2009

Become EABM
Become Reviewer

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 (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

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 9
ISSUE: 4
Year: 2009
Page: [500 - 509]
Pages: 10
DOI: 10.2174/156800909788486740
Price: $58

Article Metrics

PDF: 5