Abstract
The T cell factor 4 (Tcf-4) interacts with β-catenin in the Wnt signalling pathway and coactivates downstream target genes in diverse systems including the breast. This activity is important during normal development but its deregulation plays a pivotal role in cancer progression. In a rat model for breast cancer it has been shown that metastasis-inducing DNA (Met-DNA) sequesters the endogenous inhibitory Tcf-4 and thereby promotes transcription of the secreted extracellular matrix glycophosphoprotein, osteopontin, the direct effector of metastasis in this model system. Permanent transfection of the benign rat mammary cell line with a fragment from the Met-DNA containing the Tcf recognition sequence CAAAG induces the cells to metastasize in syngeneic rats in vivo. Tcf-4 expression in human breast carcinomas is inversely associated with osteopontin protein levels. High Tcf-4 expression impedes both OPN promoter activity and protein expression in rat mammary carcinoma cells. Understanding the role of Tcf-4 in cancer development and its transcription regulation should lay the foundation for novel therapeutic approaches in the future.
Keywords: Tcf-4, Tcf/Lef, osteopontin, Wnt signalling, target genes, cancer, metastasis, therapeutic targets, review
Current Molecular Medicine
Title: The Role of LEF/TCF Factors in Neoplastic Transformation
Volume: 8 Issue: 1
Author(s): Mohamed K. El-Tanani, Amod Ravindranath, Angeline O'Connell and Patrick G. Johnston
Affiliation:
Keywords: Tcf-4, Tcf/Lef, osteopontin, Wnt signalling, target genes, cancer, metastasis, therapeutic targets, review
Abstract: The T cell factor 4 (Tcf-4) interacts with β-catenin in the Wnt signalling pathway and coactivates downstream target genes in diverse systems including the breast. This activity is important during normal development but its deregulation plays a pivotal role in cancer progression. In a rat model for breast cancer it has been shown that metastasis-inducing DNA (Met-DNA) sequesters the endogenous inhibitory Tcf-4 and thereby promotes transcription of the secreted extracellular matrix glycophosphoprotein, osteopontin, the direct effector of metastasis in this model system. Permanent transfection of the benign rat mammary cell line with a fragment from the Met-DNA containing the Tcf recognition sequence CAAAG induces the cells to metastasize in syngeneic rats in vivo. Tcf-4 expression in human breast carcinomas is inversely associated with osteopontin protein levels. High Tcf-4 expression impedes both OPN promoter activity and protein expression in rat mammary carcinoma cells. Understanding the role of Tcf-4 in cancer development and its transcription regulation should lay the foundation for novel therapeutic approaches in the future.
Export Options
About this article
Cite this article as:
El-Tanani K. Mohamed, Ravindranath Amod, O'Connell Angeline and Johnston G. Patrick, The Role of LEF/TCF Factors in Neoplastic Transformation, Current Molecular Medicine 2008; 8 (1) . https://dx.doi.org/10.2174/156652408783565559
DOI https://dx.doi.org/10.2174/156652408783565559 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- 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
-
The Recent Electrochemical Biosensor Technologies for Monitoring of Nucleic Acid Hybridization
Current Analytical Chemistry Recent Advances in Ethnopharmacological and Toxicological Properties of Bioactive Compounds from <i>Aloe barbadensis</i> (Miller), <i>Aloe vera</i>
Current Bioactive Compounds Radiotracers in Oncology
Current Radiopharmaceuticals Epithelial Mesenchymal Transition and Cancer Stem Cell-Like Phenotypes Facilitate Chemoresistance in Recurrent Ovarian Cancer
Current Cancer Drug Targets Assays for Eukaryotic Cell Chemotaxis
Combinatorial Chemistry & High Throughput Screening Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways
Current Drug Targets Anti-Cancer/Anti-Tumor
Current Bioactive Compounds Nuclear Targeting and Retention of Anthracycline Antitumor Drugs in Sensitive and Resistant Tumor Cells
Current Medicinal Chemistry The Significance of Transferrin Receptors in Oncology: the Development of Functional Nano-based Drug Delivery Systems
Current Drug Delivery Current Trends in the Chemotherapy of Colorectal Cancer
Current Medicinal Chemistry Novel Inhibitors of Inosine Monophosphate Dehydrogenase in Patent Literature of the Last Decade
Recent Patents on Anti-Cancer Drug Discovery Recent Patents on Mesenchymal Stem Cell Mediated Therapy in Inflammatory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts
Anti-Cancer Agents in Medicinal Chemistry Evaluation of the Soluble Pectin Content in Culinary Preparations
Current Nutrition & Food Science Nanomaterials for Photohyperthermia: A Review
Current Pharmaceutical Design Apoptosis Signaling Pathways in Anticancer Therapy
Current Cancer Therapy Reviews Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents
Current Medicinal Chemistry Bisphenol A as a Factor in the Mosaic of Autoimmunity
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1): Structure-Based Design of MKP-1 Inhibitors and Upregulators
Current Medicinal Chemistry Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer
Current Topics in Medicinal Chemistry