Abstract
The aryl hydrocarbon receptor (AhR) is a ligand activated basic helix-loop-helix transcription factor that binds to environmental poly aromatic hydrocarbons (PAH) and mediates their toxic and carcinogenic responses. There is ample documentation for the role of AhR in PAH-induced carcinogenicity. However, in this report we addressed whether overexpression of AhR alone is sufficient to induce carcinogenic transformation in human mammary epithelial cells (HMEC). Retroviral expression vectors were used to develop a series of stable cell lines expressing varying levels of AhR protein in an immortalized normal HMEC with relatively low endogenous AhR expression. The resulting increase in AhR expression and activity correlated with the development of cellular malignant phenotypes, most significantly epithelial-tomesenchymal transition. Clones overexpressing AhR by more than 3-fold, exhibited a 50% decrease in population doubling time. Cell cycle analysis revealed that this increase in proliferation rates was due to an enhanced cell cycle progression by increasing the percentage of cells transiting into S- and G2/M phases. Cells overexpressing AhR exhibited enhanced motility and migration. Importantly, these cells acquired the ability to invade matrigel matrix, where more than 80% of plated cells invaded the matrigel matrix within 24 h, whereas none of parental or the vector control HMEC were able to invade matrigel. Collectively, these data provide evidence for a direct role of AhR in the progression of breast carcinoma. The results suggest a novel therapeutic target that could be considered for treatment and prevention of breast cancer progression.
Keywords: Aryl hydrocarbon receptor, ectopic overexpression, mammary epithelia, transformation, breast cancer, progression, basic helix-loop-helix, retinoblastoma, cyclin-dependent kinase, fluorescence activated cell sorter
Current Cancer Drug Targets
Title: Malignant Transformation of Mammary Epithelial Cells by Ectopic Overexpression of the Aryl Hydrocarbon Receptor
Volume: 11 Issue: 5
Author(s): J. Brooks and S. E. Eltom
Affiliation:
Keywords: Aryl hydrocarbon receptor, ectopic overexpression, mammary epithelia, transformation, breast cancer, progression, basic helix-loop-helix, retinoblastoma, cyclin-dependent kinase, fluorescence activated cell sorter
Abstract: The aryl hydrocarbon receptor (AhR) is a ligand activated basic helix-loop-helix transcription factor that binds to environmental poly aromatic hydrocarbons (PAH) and mediates their toxic and carcinogenic responses. There is ample documentation for the role of AhR in PAH-induced carcinogenicity. However, in this report we addressed whether overexpression of AhR alone is sufficient to induce carcinogenic transformation in human mammary epithelial cells (HMEC). Retroviral expression vectors were used to develop a series of stable cell lines expressing varying levels of AhR protein in an immortalized normal HMEC with relatively low endogenous AhR expression. The resulting increase in AhR expression and activity correlated with the development of cellular malignant phenotypes, most significantly epithelial-tomesenchymal transition. Clones overexpressing AhR by more than 3-fold, exhibited a 50% decrease in population doubling time. Cell cycle analysis revealed that this increase in proliferation rates was due to an enhanced cell cycle progression by increasing the percentage of cells transiting into S- and G2/M phases. Cells overexpressing AhR exhibited enhanced motility and migration. Importantly, these cells acquired the ability to invade matrigel matrix, where more than 80% of plated cells invaded the matrigel matrix within 24 h, whereas none of parental or the vector control HMEC were able to invade matrigel. Collectively, these data provide evidence for a direct role of AhR in the progression of breast carcinoma. The results suggest a novel therapeutic target that could be considered for treatment and prevention of breast cancer progression.
Export Options
About this article
Cite this article as:
Brooks J. and E. Eltom S., Malignant Transformation of Mammary Epithelial Cells by Ectopic Overexpression of the Aryl Hydrocarbon Receptor, Current Cancer Drug Targets 2011; 11 (5) . https://dx.doi.org/10.2174/156800911795655967
DOI https://dx.doi.org/10.2174/156800911795655967 |
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
-
Perspectives in Nanomedicine-Based Research Towards Cancer Therapies
Current Nanoscience Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems
Current Pharmaceutical Design Reduced Nicotinamide Adenine Dinucleotide (NADH) Fluorescence for the Detection of Cell Death
Anti-Cancer Agents in Medicinal Chemistry ImmunoPET in Neoplasms of Gastrointestinal Tract, Liver and Pancreas in the XXIst Century: Bridging the Gap Between Diagnosis and Therapy
Reviews on Recent Clinical Trials Theoretical Analysis of the Binding of Potential Inhibitors to Protein Kinases MK2 and MK3
Medicinal Chemistry How Immune-inflammatory Processes Link CNS and Psychiatric Disorders: Classification and Treatment Implications
CNS & Neurological Disorders - Drug Targets Biological Relevance of DNA Polymerase Beta and Translesion Synthesis Polymerases to Cancer and its Treatment
Current Molecular Pharmacology Palladium-Catalyzed Oxyarylation, Azaarylation and α-Arylation Reactions in the Synthesis of Bioactive Isoflavonoid Analogues
Current Organic Synthesis Glyoxalase 1 and 2 Enzyme Inhibitory Activity of 6-Sulfamoylsaccharin and Sulfocoumarin Derivates
Letters in Drug Design & Discovery Computer-Aided Drug Design of Bioactive Natural Products
Current Topics in Medicinal Chemistry Synthesis and Biological Evaluation of New Quinoline-Based Thiazolyl Hydrazone Derivatives as Potent Antifungal and Anticancer Agents
Letters in Drug Design & Discovery Lysosomal Storage Diseases and the Blood-Brain Barrier
Current Pharmaceutical Design Lymphatic Endothelial Cells, Inflammatory Lymphangiogenesis, and Prospective Players
Current Medicinal Chemistry A Fast and Efficient Chemiluminescence Method for Determination and Pharmacokinetic Study of Paclitaxel in Rat Plasma
Current Pharmaceutical Analysis The Role of Melanocortin Peptides and Receptors in Regulation of Energy Balance
Current Pharmaceutical Design Anti-cancer Effects of Metformin: Recent Evidences for its Role in Prevention and Treatment of Cancer
Current Drug Metabolism Medicinal Perspective of Indole Derivatives: Recent Developments and Structure-Activity Relationship Studies
Current Drug Targets A Review of the Current Role of Proton Therapy in Modern Oncology
Current Drug Therapy An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein
Current Cancer Drug Targets Recent Patents on the Development of c-Met Kinase Inhibitors
Recent Patents on Anti-Cancer Drug Discovery