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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- 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
-
Latest Results for Anti-Angiogenic Drugs in Cancer Treatment
Current Pharmaceutical Design Natural Products as Leads for Tuberculosis Drug Development
Current Topics in Medicinal Chemistry The ErbB Receptors and their Ligands in Cancer: An Overview
Current Drug Targets Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfβ3<sup>-/-</sup> Mouse Fetuses
MicroRNA Synthesis and Anticancer Studies of Novel N-benzyl Pyridazino ne Derivatives
Letters in Drug Design & Discovery Interplay of Carotenoids with Cigarette Smoking: Implications in Lung Cancer
Current Medicinal Chemistry Regulation of Angiogenesis by Th1- and Th2-Type Cytokines
Current Pharmaceutical Design Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy
Current Drug Metabolism Marine Food Protection in Testicular Damages Caused by Diabetes Mellitus
Current Diabetes Reviews Ribozymes, DNAzymes and Small Interfering RNAs as Therapeutics
Current Drug Targets Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-19
Current Hypertension Reviews Deep Inspiration Breath-hold (DIBH) Technique to Reduce Cardiac Radiation Dose in the Management of Breast Cancer
Current Cancer Therapy Reviews Application of Hyperthermia for Cancer Treatment: Recent Patents Review
Recent Patents on Anti-Cancer Drug Discovery ABC Transporters and the Blood-Brain Barrier
Current Pharmaceutical Design Trends in Biotechnological Drugs for Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Radiosensitization of Prostate Cancer by Soy Isoflavones
Current Cancer Drug Targets A Review of Ruthenium Complexes Activities on Breast Cancer Cells
Mini-Reviews in Medicinal Chemistry Design, Synthesis and Biological Evaluation of Salicylamide Analogues as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Letters in Drug Design & Discovery Cytotoxic Activity of Polysubstituted 7-chloro-4-quinolinylhydrazone Derivatives
Letters in Drug Design & Discovery Stearoyl-CoA Desaturase: A Vital Checkpoint in the Development and Progression of Obesity
Endocrine, Metabolic & Immune Disorders - Drug Targets