17beta-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.

Pescatori, S., Berardinelli, F., Albanesi, J., Ascenzi, P., Marino, M., Antoccia, A., et al. (2021). A Tale of Ice and Fire: The Dual Role for 17beta-Estradiol in Balancing DNA Damage and Genome Integrity. CANCERS [10.3390/cancers13071583].

A Tale of Ice and Fire: The Dual Role for 17beta-Estradiol in Balancing DNA Damage and Genome Integrity

Pescatori S
Writing – Original Draft Preparation
;
Berardinelli F
Writing – Original Draft Preparation
;
Albanesi J
Writing – Review & Editing
;
Ascenzi P
Writing – Review & Editing
;
Marino M
Writing – Review & Editing
;
Antoccia A
Writing – Review & Editing
;
di Masi A
Writing – Review & Editing
;
Acconcia F
Writing – Review & Editing
2021

Abstract

17beta-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.
Pescatori, S., Berardinelli, F., Albanesi, J., Ascenzi, P., Marino, M., Antoccia, A., et al. (2021). A Tale of Ice and Fire: The Dual Role for 17beta-Estradiol in Balancing DNA Damage and Genome Integrity. CANCERS [10.3390/cancers13071583].
File in questo prodotto:
File Dimensione Formato  
Pescatori21.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.95 MB
Formato Adobe PDF
1.95 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11590/385825
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact