Abstract
Local estrogen production from aromatase-mediated conversion of androgens is an important mechanism of autocrine growth stimulation in hormone-dependent breast cancers. The control mechanism of aromatase enzymatic activity in recent years has been demonstrated to be more complex than previously identified. Indeed, it is well known that aromatase expression is regulated at the transcriptional level through the alternative use of tissue-specific promoters, whereas it has become clear that the activity of this enzyme is also controlled by post-transcriptional modifications, such as phosphorylation processes. This paper presents a selective review of the novel findings in this area showing phosphorylation/dephosphorylation of aromatase as a switch to rapidly modulate its enzymatic activity. Particularly, we describe studies conducted in our laboratories, focusing on the role of estrogens in modulating aromatase activity in estrogen-dependent breast cancer cells. Two separate mechanisms are described. First, 17β-estradiol (E2), through c-Src kinase, is able to enhance tyrosine phosphorylation levels of aromatase protein and increases its enzymatic activity and estrogen biosynthesis. Secondly, E2, through the activation of PI3K/Akt pathway, impairs the ability of the tyrosine phosphatase PTP1B to dephosphorylate aromatase, resulting in a consequent enhanced phosphorylation and activity of the aromatase protein itself. These new controls of aromatase function provide insights into the mechanisms through which local estrogen production can be altered in breast cancer tissues. They also offer a vast array of possibilities for identifying different cell signalings that should be targeted in novel therapeutic strategies for breast cancer treatment.
Keywords: Aromatase, breast cancer, c-Src, estrogen receptor, PTP1B, tyrosine phosphorylation.
Mini-Reviews in Medicinal Chemistry
Title:Phosphorylation Processes Controlling Aromatase Activity in Br east Cancer: An Update
Volume: 16 Issue: 9
Author(s): Stefania Catalano, Ines Barone, Stefania Marsico, Rosalinda Bruno and Sebastiano Andò
Affiliation:
Keywords: Aromatase, breast cancer, c-Src, estrogen receptor, PTP1B, tyrosine phosphorylation.
Abstract: Local estrogen production from aromatase-mediated conversion of androgens is an important mechanism of autocrine growth stimulation in hormone-dependent breast cancers. The control mechanism of aromatase enzymatic activity in recent years has been demonstrated to be more complex than previously identified. Indeed, it is well known that aromatase expression is regulated at the transcriptional level through the alternative use of tissue-specific promoters, whereas it has become clear that the activity of this enzyme is also controlled by post-transcriptional modifications, such as phosphorylation processes. This paper presents a selective review of the novel findings in this area showing phosphorylation/dephosphorylation of aromatase as a switch to rapidly modulate its enzymatic activity. Particularly, we describe studies conducted in our laboratories, focusing on the role of estrogens in modulating aromatase activity in estrogen-dependent breast cancer cells. Two separate mechanisms are described. First, 17β-estradiol (E2), through c-Src kinase, is able to enhance tyrosine phosphorylation levels of aromatase protein and increases its enzymatic activity and estrogen biosynthesis. Secondly, E2, through the activation of PI3K/Akt pathway, impairs the ability of the tyrosine phosphatase PTP1B to dephosphorylate aromatase, resulting in a consequent enhanced phosphorylation and activity of the aromatase protein itself. These new controls of aromatase function provide insights into the mechanisms through which local estrogen production can be altered in breast cancer tissues. They also offer a vast array of possibilities for identifying different cell signalings that should be targeted in novel therapeutic strategies for breast cancer treatment.
Export Options
About this article
Cite this article as:
Catalano Stefania, Barone Ines, Marsico Stefania, Bruno Rosalinda and Andò Sebastiano, Phosphorylation Processes Controlling Aromatase Activity in Br east Cancer: An Update, Mini-Reviews in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1389557516666160321113041
DOI https://dx.doi.org/10.2174/1389557516666160321113041 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
Targeting CD147 is a Novel Strategy for Antitumor Therapy
Current Pharmaceutical Design Peripherally Located A431 Cells are More Sensitive to Cell Death Induced by Exogenous Oxidative Stress
Current Signal Transduction Therapy microRNAs Downregulation in Cancer is Associated with Guanine Enrichment in the Terminal Loop Sequences of their Precursors
MicroRNA 6-Chloro-7-methyl-3', 4'-dimethoxyflavone – a Potent Selective COX-2 Inhibitor
Medicinal Chemistry Transcriptional Regulation by Promoter Targeted RNAs
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Gene Therapy for Gastrointestinal and Liver Cancers: Past Experience, Current Status and Future Perspectives)
Current Gene Therapy Based on Nucleotides Analysis of Tumor Cell Lines to Construct and Validate a Prediction Model of Mechanisms of Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Editorial from Guest Editor [Hot Topic: Familial and Hereditary Breast and Ovarian Tumors (Guest Editors: Antonio Russo and Massimo Federico)]
Current Women`s Health Reviews Macrophages in Immunopathology of Atherosclerosis: A Target for Diagnostics and Therapy
Current Pharmaceutical Design Valproic Acid As Anti-Cancer Drug
Current Pharmaceutical Design Enteric Coated Guar Gum Microspheres of Ornidazole for Colonic Delivery
Current Nanoscience STAT3 as a Central Regulator of Tumor Metastases
Current Molecular Medicine Advancement in Microbial Cheminformatics
Current Topics in Medicinal Chemistry Use of Artificial Cell Microcapsule Containing Thalidomide for Treating TNBS-induced Crohn's Disease in Mice
Current Drug Delivery Himalayan Plants as a Source of Anti-Cancer Agents: A Review
The Natural Products Journal Bioactive Proteins and Peptides from Soybeans
Recent Patents on Food, Nutrition & Agriculture Editorial (Another Year of Prosperity for Current Molecular Medicine)
Current Molecular Medicine Effects of Lipid-Lowering Drugs on Adiponectin
Current Vascular Pharmacology Radiobromine-Labelled Tracers for Positron Emission Tomography: Possibilities and Pitfalls
Current Radiopharmaceuticals Low Molecular Weight and Oligomeric Chitosans and Their Bioactivities
Current Topics in Medicinal Chemistry