Abstract
1α,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the most active metabolite of vitamin D, exerts its biological effects by binding to a specific intracellular receptor (the vitamin D receptor, VDR) present in target cells. 1,25-(OH)2D3 is involved in a host of cell processes, including calcium homeostasis, cell growth and differentiation, and secretion of hormones. Several studies have explored the role of 1,25-(OH)2D3 in cell growth and differentiation in normal and tumoral mammary gland, in which it shows antiproliferative effects. These effects have been attributed to suppression of growth-stimulatory signals and potentiation of growth-inhibitory signals, leading to changes in cell-cycle regulators as well as to induction of apoptosis. In apparent contrast to these antiproliferative effects, however, several studies have suggested that breast tumor formation may be related to the autocrine/paracrine effects of growth hormone (GH) and prolactin (PRL). The pituitary transcription factor-1 (Pit-1), which in the pituitary is critical to both cell differentiation and PRL and GH transcription, has been recently found in normal and tumoral human breast tissue, with mRNA expression levels significantly higher in tumors than in normal breast. As in the pituitary, Pit-1 regulates mammary GH and PRL secretion, increases cell proliferation and decreases apoptosis. 1,25-(OH)2D3 administration to the MCF-7 human breast adenocarcinoma cell line significantly reduces Pit-1 expression, suggesting that inhibition of Pit-1 expression by 1,25-(OH)2D3 may reduce the increase in proliferation induced by this transcription factor directly or indirectly through increased GH and/or PRL expression. In this review, we evaluate the role of 1,25-(OH)2D3 and Pit- 1/PRL/GH in human breast, and consider the relationships between these factors in normal mammary development and in breast cancer.
Keywords: Pituitary transcription factor-1, Pit-1, vitamin D, VDR, PRL, GH, breast cancer
Current Medicinal Chemistry
Title: Vitamin D, Pit-1, GH, and PRL: Possible Roles in Breast Cancer Development
Volume: 14 Issue: 29
Author(s): R. Perez-Fernandez, S. Seoane, T. Garcia-Caballero, C. Segura and M. Macia
Affiliation:
Keywords: Pituitary transcription factor-1, Pit-1, vitamin D, VDR, PRL, GH, breast cancer
Abstract: 1α,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the most active metabolite of vitamin D, exerts its biological effects by binding to a specific intracellular receptor (the vitamin D receptor, VDR) present in target cells. 1,25-(OH)2D3 is involved in a host of cell processes, including calcium homeostasis, cell growth and differentiation, and secretion of hormones. Several studies have explored the role of 1,25-(OH)2D3 in cell growth and differentiation in normal and tumoral mammary gland, in which it shows antiproliferative effects. These effects have been attributed to suppression of growth-stimulatory signals and potentiation of growth-inhibitory signals, leading to changes in cell-cycle regulators as well as to induction of apoptosis. In apparent contrast to these antiproliferative effects, however, several studies have suggested that breast tumor formation may be related to the autocrine/paracrine effects of growth hormone (GH) and prolactin (PRL). The pituitary transcription factor-1 (Pit-1), which in the pituitary is critical to both cell differentiation and PRL and GH transcription, has been recently found in normal and tumoral human breast tissue, with mRNA expression levels significantly higher in tumors than in normal breast. As in the pituitary, Pit-1 regulates mammary GH and PRL secretion, increases cell proliferation and decreases apoptosis. 1,25-(OH)2D3 administration to the MCF-7 human breast adenocarcinoma cell line significantly reduces Pit-1 expression, suggesting that inhibition of Pit-1 expression by 1,25-(OH)2D3 may reduce the increase in proliferation induced by this transcription factor directly or indirectly through increased GH and/or PRL expression. In this review, we evaluate the role of 1,25-(OH)2D3 and Pit- 1/PRL/GH in human breast, and consider the relationships between these factors in normal mammary development and in breast cancer.
Export Options
About this article
Cite this article as:
Perez-Fernandez R., Seoane S., Garcia-Caballero T., Segura C. and Macia M., Vitamin D, Pit-1, GH, and PRL: Possible Roles in Breast Cancer Development, Current Medicinal Chemistry 2007; 14 (29) . https://dx.doi.org/10.2174/092986707782793943
DOI https://dx.doi.org/10.2174/092986707782793943 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Recent Clinical Experience with Oncolytic Viruses
Current Pharmaceutical Biotechnology Comparison of the Effects of Diltiazem Gel with Lidocaine Gel on Reducing Pain and Discomfort in Patients Undergoing Rectosigmoidoscopy: A Randomized Double-blinded Clinical Trial
Current Drug Therapy Arylurea Derivatives: A Class of Potential Cancer Targeting Agents
Current Topics in Medicinal Chemistry Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer
Current Protein & Peptide Science Structural Insights for Drugs Developed for Phospholipase D Enzymes
Current Drug Discovery Technologies Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer
Current Cancer Drug Targets Epigenetic Modulation: A Promising Avenue to Advance Hematopoietic Stem Cell-Based Therapy for Severe Autoimmune Disorders
Epigenetic Diagnosis & Therapy (Discontinued) Non-Invasive Cell Tracking in Cancer and Cancer Therapy
Current Topics in Medicinal Chemistry Denoising Medical Images Using Machine Learning, Deep Learning Approaches: A Survey
Current Medical Imaging In-Gel Protein Phosphatase Assays and Other Useful Methods for the Detection of Protein Phosphatase Activities
Anti-Cancer Agents in Medicinal Chemistry Management of Vaginal Cancer
Reviews on Recent Clinical Trials Ghrelin: A Molecular Target for Weight Regulation, Glucose and Lipid Metabolism
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer
Current Cancer Drug Targets Routine Collection of Patient-Reported Outcomes in an HIV Clinic Setting:The First 100 Patients
Current HIV Research Rheumatology: A Force for Change in Monoclonal Antibodies
Current Pharmaceutical Design Human Arylamine N-Acetyltransferase 1: A Drug-Metabolizing Enzyme and a Drug Target?
Current Drug Targets Targeting Telomerase for Cancer Therapy
Current Cancer Therapy Reviews Trends and Applications of Brain Computer Interfaces
Current Signal Transduction Therapy Strategies for Preparing Different Types of Lipid Polymer Hybrid Nanoparticles in Targeted Tumor Therapy
Current Pharmaceutical Design Estrogen Receptor: Structural Differences and Potential Implications on Selectivity Examined by the GRID/CPCA Approach
Letters in Drug Design & Discovery