Abstract
Adenocarcinoma of the prostate is the most common type of cancer, excluding skin cancer, and the second leading cause of cancer death in adult men in the United States. The lifetime risk for developing symptomatic prostate cancer is one in five for an American man. A pivotal step in carcinogenesis is a shift in the balance between proliferation, differentiation, and apoptosis that favors cell proliferation. Transforming growth factor-ß (TGF-ß) is a key negative growth regulator in the normal prostate. Although TGF-ß inhibits the proliferation of normal prostate cells and functions as a tumor suppressor in early tumorigenesis, it acts as a tumor promoter in later stages of tumor progression. Elevated expression of TGF-ß in prostate cancer cells is associated with poor clinical outcome. Over-expression of TGF-ß aids tumorigenesis by not only stimulating angiogenesis and suppressing the immune system, but also by acting directly on the prostate tumor cells. While prostate cancer cells become resistant to TGF-ß-induced growth inhibition and apoptosis, they retain other TGF-ß-induced responses that enhance tumorgenicity, such as induction of extracellular matrix proteins, cell adhesion proteins and proteases. These direct tumor effects are mediated primarily through Smad signaling. This review addresses the mechanisms by which prostate cancer cells may acquire TGF-ß resistance and promote tumorgenicity. Understanding the mechanisms underlying TGF-ß resistance is important for the identification and development of better diagnostic markers and more effective strategies for treating prostate cancer.
Keywords: prostate cancer, smad, tgf, receptor
Current Drug Targets
Title: TGF-ß / Smad Signaling in Prostate Cancer
Volume: 4 Issue: 3
Author(s): Diana Bello-DeOcampo and Donald J. Tindall
Affiliation:
Keywords: prostate cancer, smad, tgf, receptor
Abstract: Adenocarcinoma of the prostate is the most common type of cancer, excluding skin cancer, and the second leading cause of cancer death in adult men in the United States. The lifetime risk for developing symptomatic prostate cancer is one in five for an American man. A pivotal step in carcinogenesis is a shift in the balance between proliferation, differentiation, and apoptosis that favors cell proliferation. Transforming growth factor-ß (TGF-ß) is a key negative growth regulator in the normal prostate. Although TGF-ß inhibits the proliferation of normal prostate cells and functions as a tumor suppressor in early tumorigenesis, it acts as a tumor promoter in later stages of tumor progression. Elevated expression of TGF-ß in prostate cancer cells is associated with poor clinical outcome. Over-expression of TGF-ß aids tumorigenesis by not only stimulating angiogenesis and suppressing the immune system, but also by acting directly on the prostate tumor cells. While prostate cancer cells become resistant to TGF-ß-induced growth inhibition and apoptosis, they retain other TGF-ß-induced responses that enhance tumorgenicity, such as induction of extracellular matrix proteins, cell adhesion proteins and proteases. These direct tumor effects are mediated primarily through Smad signaling. This review addresses the mechanisms by which prostate cancer cells may acquire TGF-ß resistance and promote tumorgenicity. Understanding the mechanisms underlying TGF-ß resistance is important for the identification and development of better diagnostic markers and more effective strategies for treating prostate cancer.
Export Options
About this article
Cite this article as:
Bello-DeOcampo Diana and Tindall J. Donald, TGF-ß / Smad Signaling in Prostate Cancer, Current Drug Targets 2003; 4 (3) . https://dx.doi.org/10.2174/1389450033491118
DOI https://dx.doi.org/10.2174/1389450033491118 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Related Books
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Advances in Human Cytochrome P450 and Personalized Medicine
Current Drug Metabolism Transmembrane Protein 166 and its Significance
Protein & Peptide Letters Mesenchymal Stem Cells: An Emerging Tool for Cancer Targeting and Therapy
Current Stem Cell Research & Therapy Methylenedioxy- and Ethylenedioxy-Fused Indolocarbazoles: Potent Human Topoisomerase I Inhibitors and Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting
Current Pharmaceutical Biotechnology Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders
Current Neuropharmacology Calcium-calpain Dependent Pathways Regulate Vesiculation in Malignant Breast Cells
Current Cancer Drug Targets Caveolae and Caveolin-1: Novel Potential Targets for the Treatment of Cardiovascular Disease
Current Pharmaceutical Design PET and PET/CT: Conceptions, Misconceptions, and a Potential New Paradigm for Enhanced Metabolic Imaging
Current Medical Imaging Anticancer Activities of New N-hetaryl-2-cyanoacetamide Derivatives Incorporating 4,5,6,7-Tetrahydrobenzo[b]thiophene Moiety
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs in Human Diseases
Recent Patents on DNA & Gene Sequences Anticancer Natural Coumarins as Lead Compounds for the Discovery of New Drugs
Current Topics in Medicinal Chemistry Modulation of ABC Transporters by Nuclear Receptors: Physiological, Pathological and Pharmacological Aspects
Current Medicinal Chemistry Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer
Current Pharmaceutical Design Molecular Modeling Based Synthesis and Evaluation of <i>In vitro</i> Anticancer Activity of Indolyl Chalcones
Current Topics in Medicinal Chemistry Is there a Rational Approach for Increasing Drug Specificity? Considerations on CNS Target Choice and Validation
Recent Patents on CNS Drug Discovery (Discontinued) Hormonal Effects on Drug Metabolism Through the CYP System: Perspectives on Their Potential Significance in the Era of Pharmacogenomics
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Ultrasensitive Electrochemical Sensors for PSA Detection: Related Surface Functionalization Strategies
Current Topics in Medicinal Chemistry Editorial: (Pharmaco)Metabolomics in Drug Discovery and Individualisation of Treatment
Current Pharmaceutical Design Advances in Methods for Therapeutic Peptide Discovery, Design and Development
Current Pharmaceutical Biotechnology