Abstract
A majority of breast cancers (BC) display characteristics of epithelial cells and express estrogen receptors and/or HER-2 (a member of the epidermal growth factor receptor family). About one-fifth of BC is constituted of basal cells for which there is no specific category of proliferation regulators. Insulin-like growth factor (IGF) signaling is involved in most BC cells, irrespective of cell type. All inducers of cell proliferation employ transcriptional as well as non-transcriptional mechanisms to activate the cascade of cyclindependent kinases, which causes irreversible progression to the G1/S phase transition. We analyze the pathways of the different inducers that lead to this cascade. Several actors in the mitogenic signal transduction are required irrespective of the initial signal although their functions may differ: for example members of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) cascades. As some of these proteins are also involved in the cell survival mechanisms, they appear to be good targets for therapeutic intervention. In the case of the estrogen-dependent cells, complex interplay between the estrogen receptor (a conditional transcription factor), co-repressors and co-activators offers additional molecular targets for therapy. Besides, we have found that p21WAF1, an inhibitor of cyclin-dependent kinases, can orient the cell to either proliferation or differentiation suggesting that at an early stage of BC development it may be possible to reverse the cellular changes associated with malignant transformation.
Keywords: Endocrine therapy, estrogens, growth factors, HER, IGF, receptors, kinases, signaling pathways
Anti-Cancer Agents in Medicinal Chemistry
Title: Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy
Volume: 8 Issue: 8
Author(s): J. Mester and G. Redeuilh
Affiliation:
Keywords: Endocrine therapy, estrogens, growth factors, HER, IGF, receptors, kinases, signaling pathways
Abstract: A majority of breast cancers (BC) display characteristics of epithelial cells and express estrogen receptors and/or HER-2 (a member of the epidermal growth factor receptor family). About one-fifth of BC is constituted of basal cells for which there is no specific category of proliferation regulators. Insulin-like growth factor (IGF) signaling is involved in most BC cells, irrespective of cell type. All inducers of cell proliferation employ transcriptional as well as non-transcriptional mechanisms to activate the cascade of cyclindependent kinases, which causes irreversible progression to the G1/S phase transition. We analyze the pathways of the different inducers that lead to this cascade. Several actors in the mitogenic signal transduction are required irrespective of the initial signal although their functions may differ: for example members of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) cascades. As some of these proteins are also involved in the cell survival mechanisms, they appear to be good targets for therapeutic intervention. In the case of the estrogen-dependent cells, complex interplay between the estrogen receptor (a conditional transcription factor), co-repressors and co-activators offers additional molecular targets for therapy. Besides, we have found that p21WAF1, an inhibitor of cyclin-dependent kinases, can orient the cell to either proliferation or differentiation suggesting that at an early stage of BC development it may be possible to reverse the cellular changes associated with malignant transformation.
Export Options
About this article
Cite this article as:
Mester J. and Redeuilh G., Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (8) . https://dx.doi.org/10.2174/187152008786847747
DOI https://dx.doi.org/10.2174/187152008786847747 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Natural Carriers for siRNA Delivery
Current Pharmaceutical Design MRI of the Small and Large Bowel
Current Medical Imaging An Automated High-Throughput Sample Preparation Protocol for LC-MS/MS Analysis of Glycopeptides
Current Proteomics Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms
Mini-Reviews in Medicinal Chemistry Antiangiogenesis Drug Design: Multiple Pathways Targeting Tumor Vasculature
Current Medicinal Chemistry Proteins as Alternate Targets of Enediynes
Letters in Drug Design & Discovery Structural Effects of TiO2 Nanoparticles and Doxorubicin on DNA and their Antiproliferative Roles in T47D and MCF7 Cells
Anti-Cancer Agents in Medicinal Chemistry Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer
Current Genomics Mevalonate Pathway and Human Cancers
Current Molecular Pharmacology Preparation and Surface Modification of Polymeric Nanoparticles for Drug Delivery: State of the Art
Recent Patents on Drug Delivery & Formulation Histamine and Histaminergic Receptors in Colorectal Cancer: From Basic Science to Evidence-based Medicine
Anti-Cancer Agents in Medicinal Chemistry Multi-Class Breast Cancer Classification Using Ensemble of Pretrained models and Transfer Learning
Current Medical Imaging Activation of Intrinsic Apoptosis and G1 Cell Cycle Arrest by a Triazole Precursor, N-(4-chlorophenyl)-2-(4-(3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide in Breast Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Systemic Delivery and Quantification of Unformulated Interfering RNAs In Vivo
Current Topics in Medicinal Chemistry Bioinformatics Approaches for Anti-cancer Drug Discovery
Current Drug Targets TSC-22 (TGF-β Stimulated Clone-22): A Novel Molecular Target for Differentiation-Inducing Therapy in Salivary Gland Cancer
Current Cancer Drug Targets Vitamin D and Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease
Cardiovascular & Hematological Disorders-Drug Targets Design, Synthesis, and Biological Evaluation of New Azole Derivatives as Potent Aromatase Inhibitors with Potential Effects against Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Novel Indole-Isoxazole Hybrids: Synthesis and In Vitro Anti-Cholinesterase Activity
Letters in Drug Design & Discovery A Review on Mechanisms of Anti Tumor Activity of Chalcones
Anti-Cancer Agents in Medicinal Chemistry