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A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity
SIMPLE SUMMARY: Paradoxically, although the steroid hormone 17β-estradiol (E2) regulates many aspects of male and female physiology, it is described in the chemical indexes as a carcinogen. By the analysis of the literature, we unveil here a novel concept for which E2 possesses a dual nature for whi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036963/ https://www.ncbi.nlm.nih.gov/pubmed/33808099 http://dx.doi.org/10.3390/cancers13071583 |
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author | Pescatori, Sara Berardinelli, Francesco Albanesi, Jacopo Ascenzi, Paolo Marino, Maria Antoccia, Antonio di Masi, Alessandra Acconcia, Filippo |
author_facet | Pescatori, Sara Berardinelli, Francesco Albanesi, Jacopo Ascenzi, Paolo Marino, Maria Antoccia, Antonio di Masi, Alessandra Acconcia, Filippo |
author_sort | Pescatori, Sara |
collection | PubMed |
description | SIMPLE SUMMARY: Paradoxically, although the steroid hormone 17β-estradiol (E2) regulates many aspects of male and female physiology, it is described in the chemical indexes as a carcinogen. By the analysis of the literature, we unveil here a novel concept for which E2 possesses a dual nature for which it is both a toxic and a homeostatic regulator controlling DNA stability. Therefore, cancer could arise as a consequence of the deregulation of this delicate equilibrium between cellular pathways. ABSTRACT: 17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects. |
format | Online Article Text |
id | pubmed-8036963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80369632021-04-12 A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity Pescatori, Sara Berardinelli, Francesco Albanesi, Jacopo Ascenzi, Paolo Marino, Maria Antoccia, Antonio di Masi, Alessandra Acconcia, Filippo Cancers (Basel) Review SIMPLE SUMMARY: Paradoxically, although the steroid hormone 17β-estradiol (E2) regulates many aspects of male and female physiology, it is described in the chemical indexes as a carcinogen. By the analysis of the literature, we unveil here a novel concept for which E2 possesses a dual nature for which it is both a toxic and a homeostatic regulator controlling DNA stability. Therefore, cancer could arise as a consequence of the deregulation of this delicate equilibrium between cellular pathways. ABSTRACT: 17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects. MDPI 2021-03-30 /pmc/articles/PMC8036963/ /pubmed/33808099 http://dx.doi.org/10.3390/cancers13071583 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Review Pescatori, Sara Berardinelli, Francesco Albanesi, Jacopo Ascenzi, Paolo Marino, Maria Antoccia, Antonio di Masi, Alessandra Acconcia, Filippo A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title | A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title_full | A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title_fullStr | A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title_full_unstemmed | A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title_short | A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity |
title_sort | tale of ice and fire: the dual role for 17β-estradiol in balancing dna damage and genome integrity |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036963/ https://www.ncbi.nlm.nih.gov/pubmed/33808099 http://dx.doi.org/10.3390/cancers13071583 |
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