Abstract
Prostate cancer is initially dependent on androgens for growth; hence, recurrent prostate is treated with androgen ablation which may result in progression to androgen independence characterized by a resistance to such therapy. Androgens bind to and activate the androgen receptor (AR), a member of the nuclear steroid receptor family of transcription factors, which regulates prostate cancer cell proliferation and survival in androgen-independent, as well as -dependent, tumors. Another pathway regulating proliferation and survival is the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Here we analyze reports in the literature indicating that these two pathways cooperate to regulate prostate tumor development and progression. Studies show that AR transcriptional activity and expression are regulated by Akt. In addition, androgens regulate the Akt pathway by both genomic and non-genomic effects. This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3β/β-catenin pathway, NF-βB, and the FOXO family of transcription factors, will be discussed. In addition, we will discuss the role of Akt in the interaction of the AR with upstream regulators of Akt phosphorylation, such as receptor tyrosine kinases of the EGF and IGF-1 receptor families and the tumor suppressor PTEN.
Keywords: Prostate cancer, androgen receptor, Akt, hormone dependence
Current Cancer Drug Targets
Title: Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer
Volume: 7 Issue: 6
Author(s): Yu Wang, Jeffrey I. Kreisberg and Paramita M. Ghosh
Affiliation:
Keywords: Prostate cancer, androgen receptor, Akt, hormone dependence
Abstract: Prostate cancer is initially dependent on androgens for growth; hence, recurrent prostate is treated with androgen ablation which may result in progression to androgen independence characterized by a resistance to such therapy. Androgens bind to and activate the androgen receptor (AR), a member of the nuclear steroid receptor family of transcription factors, which regulates prostate cancer cell proliferation and survival in androgen-independent, as well as -dependent, tumors. Another pathway regulating proliferation and survival is the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Here we analyze reports in the literature indicating that these two pathways cooperate to regulate prostate tumor development and progression. Studies show that AR transcriptional activity and expression are regulated by Akt. In addition, androgens regulate the Akt pathway by both genomic and non-genomic effects. This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3β/β-catenin pathway, NF-βB, and the FOXO family of transcription factors, will be discussed. In addition, we will discuss the role of Akt in the interaction of the AR with upstream regulators of Akt phosphorylation, such as receptor tyrosine kinases of the EGF and IGF-1 receptor families and the tumor suppressor PTEN.
Export Options
About this article
Cite this article as:
Wang Yu, Kreisberg I. Jeffrey and Ghosh M. Paramita, Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer, Current Cancer Drug Targets 2007; 7 (6) . https://dx.doi.org/10.2174/156800907781662248
DOI https://dx.doi.org/10.2174/156800907781662248 |
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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
![](/images/wayfinder.jpg)
- 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
-
Synthesis and Stereochemistry-Activity Relationship of Chiral Thiourea Derivatives as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Cytotoxic and Allergenic Potential of Bioactive Proteins and Peptides
Current Pharmaceutical Design Different Gene Therapy Strategies: A Overview for Prostate Cancer
Current Gene Therapy Design, Synthesis and Evaluation of Peroxisome Proliferator-Activated Receptor α/βDual Agonists for the Treatment of Type 2 Diabetes
Letters in Drug Design & Discovery Meet Our Editorial Board Member
Current Signal Transduction Therapy Progress in the Development of Selective Inhibitors of Aurora Kinases
Current Topics in Medicinal Chemistry DNA Double Strand Breaks Repair Inhibitors: Relevance as Potential New Anticancer Therapeutics
Current Medicinal Chemistry Epigenetic Targeting of Platinum Resistant Testicular Cancer
Current Cancer Drug Targets Nuclear Imaging of Hormonal Receptor Status in Breast Cancer: A Tool for Guiding Endocrine Treatment and Drug Development
Current Cancer Drug Targets Lung Cancer Chemotherapy, New Treatment and Related Patents
Recent Patents on Anti-Cancer Drug Discovery Last Findings on Dual Inhibitors of Abl and Src Tyrosine-Kinases
Mini-Reviews in Medicinal Chemistry Therapeutic Potential of Targeting Transforming Growth Factor-beta in Colorectal Cancer: Rational and Progress
Current Pharmaceutical Design p53 is an Important Regulator of CCL2 Gene Expression
Current Molecular Medicine Current Development of ROS-Modulating Agents as Novel Antitumor Therapy
Current Cancer Drug Targets Treating Benign Prostatic Hyperplasia with Botulinum Neurotoxin
Current Medicinal Chemistry Cognitive Impacts of Estrogen Treatment in Androgen-Deprived Males: What Needs to be Resolved
Current Neuropharmacology EGFR Transactivation by Peptide G Protein-Coupled Receptors in Cancer
Current Drug Targets 5-Lipoxygenase in the Central Nervous System: Therapeutic Implications
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Epithelial-Mesenchymal Plasticity of Breast Cancer Stem Cells: Implications for Metastasis and Therapeutic Resistance
Current Pharmaceutical Design Molecular Modeling Applied to Anti-Cancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry