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 |

- 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
- Announcements
Related Articles
-
Meet Our Editorial Board Member
Current Cancer Therapy Reviews Bangladeshi Medicinal Plant Extracts Inhibiting Molecular Interactions between Nuclear Factors and Target DNA Sequences Mimicking NF-kB Binding Sites
Medicinal Chemistry Characterization and Immunological Evaluation of Low-Molecular- Weight Alginate Derivatives
Current Topics in Medicinal Chemistry Malignant Glioma In Vitro Models: On the Utilization of Stem-like Cells
Current Cancer Drug Targets Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy
Current Cancer Drug Targets Secretory Clusterin: A Promising Target for Chemoresistance of Hepatocellular Carcinoma
Mini-Reviews in Medicinal Chemistry Oncologic Imaging End-Points for the Assessment of Therapy Response
Recent Patents on Anti-Cancer Drug Discovery Anti-breast Cancer Potential of Natural and Synthetic Coumarin Derivatives
Current Topics in Medicinal Chemistry Proinflammatory Cytokines in Breast Cancer: Mechanisms of Action and Potential Targets for Therapeutics
Current Drug Targets Synthesis and Clinical Development of Palbociclib: An Overview
Medicinal Chemistry PPARs in Diseases: Control Mechanisms of Inflammation
Current Medicinal Chemistry Periplogenin Activates ROS-ER Stress Pathway to Trigger Apoptosis via BIP-eIF2α- CHOP and IRE1α-ASK1-JNK Signaling Routes
Anti-Cancer Agents in Medicinal Chemistry Withdrawal Notice: Application of Nanomaterials in Development of Electrochemical Sensors and Drug Delivery Systems for Anticancer Drugs
Current Drug Delivery Receptor Tyrosine Kinases as Therapeutic Targets the Model of the MET Oncogene
Current Drug Targets Gene Expression Profiles in Breast Cancer to Identify Estrogen Receptor Target Genes
Mini-Reviews in Medicinal Chemistry Breakfast and Learning: An Updated Review
Current Nutrition & Food Science Potential Cardio-Protective Agents: A Resveratrol Review (2000-2019)
Current Pharmaceutical Design Strategies of Engineering Nanoparticles for Treating Neurodegenerative Disorders
Current Drug Metabolism NBN Polymorphysms and Cancer Susceptibility: A Systematic Review
Current Genomics Simultaneous UPLC-MS/MS Determination of 6-mercaptopurine, 6-methylmercaptopurine and 6-thioguanine in Plasma: Application to the Pharmacokinetic Evaluation of Novel Dosage forms in Beagle Dogs
Current Pharmaceutical Design