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
Current Cancer Drug Targets
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
Volume: 9 Issue: 4
Author(s): Jin Ding, Beifang Ning, Yi Huang, Dongyun Zhang, Jingxia Li, Chang-Yan Chen and Chuanshu Huang
Affiliation:
Keywords: PI-3K, Akt, JNK, c-Jun, cyclin D1, arsenite, cell proliferation
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.
Export Options
About this article
Cite this article as:
Ding Jin, Ning Beifang, Huang Yi, Zhang Dongyun, Li Jingxia, Chen Chang-Yan and Huang Chuanshu, PI3K/Akt/JNK/c-Jun Signaling Pathway is a Mediator for Arsenite- Induced Cyclin D1 Expression and Cell Growth in Human Bronchial Epithelial Cells, Current Cancer Drug Targets 2009; 9 (4) . https://dx.doi.org/10.2174/156800909788486740
DOI https://dx.doi.org/10.2174/156800909788486740 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Current Role of Proteomics in Pancreatic Cancer Biomarkers Research
Current Proteomics Preclinical Evidence on the Anticancer Properties of Food Peptides
Protein & Peptide Letters Volatile Disease Biomarkers in Breath: A Critique
Current Pharmaceutical Biotechnology Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery Blending of Polyethylenimine with a Cationic Polyurethane Greatly Enhances Both DNA Delivery Efficacy and Reduces the Overall Cytotoxicity
Current Pharmaceutical Biotechnology AMPK: Therapeutic Target for Diabetes and Cancer Prevention
Current Pharmaceutical Design Carbonic Anhydrase Inhibitors and the Management of Cancer
Current Topics in Medicinal Chemistry G-Quadruplex Interacting Agents Targeting the Telomeric G-Overhang Are More than Simple Telomerase Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents Cytotoxic Properties of Clofibrate and other Peroxisome Proliferators: Relevance to Cancer Progression
Current Medicinal Chemistry Current Landscape of Natural Products against Coronaviruses: Perspectives in COVID-19 Treatment and Anti-viral Mechanism
Current Pharmaceutical Design Bioactivity of Chitosan and Its Derivatives
Current Organic Chemistry Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF
Current Cancer Drug Targets Immunomodulation Via Targeted Inhibition of Antigen Receptor Signal Transduction
Cardiovascular & Hematological Disorders-Drug Targets Unravelling the Genetic Susceptibility to Develop Ligament and Tendon Injuries
Current Stem Cell Research & Therapy Functions of Polo-Like Kinases: A Journey From Yeast To Humans
Protein & Peptide Letters In Search of Natural Remediation for Cervical Cancer
Anti-Cancer Agents in Medicinal Chemistry Targeting Different Signaling Pathways with Antisense Oligonucleotides Combination for Cancer Therapy
Current Pharmaceutical Design Efficacy and Cardiovascular Safety of Insulins
Current Drug Safety Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches
Current Pharmaceutical Design