Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress.
Animals
Apoptosis
/ genetics
Carcinogenesis
/ pathology
DNA Damage
/ radiation effects
DNA Repair
/ genetics
DNA-Binding Proteins
/ genetics
Epidermis
/ pathology
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Keratinocytes
/ pathology
Keratosis, Actinic
/ etiology
Mice
Mice, Knockout
Neoplasms, Experimental
/ etiology
Oxidative Stress
/ genetics
Skin Neoplasms
/ etiology
Ultraviolet Rays
/ adverse effects
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
08
10
2018
revised:
09
01
2019
accepted:
23
01
2019
pubmed:
18
3
2019
medline:
17
6
2020
entrez:
18
3
2019
Statut:
ppublish
Résumé
HIF-1α is constitutively expressed in mouse and human epidermis. It plays a crucial role in skin physiology, including the response of keratinocytes to UVR. However, little information is available about its role in photocarcinogenesis. Using a multistage model of UVB radiation-induced skin cancer, we show that the knockout of Hif-1α in the epidermis prevents tumorigenesis but at the same time triggers the formation of hyperkeratotic plaques. Our results indicate that the absence of oncogenic transformation in Hif-1α-ablated mice is related to increased DNA repair in keratinocytes, whereas the formation of hyperkeratotic plaques is caused by an increase in the levels of reactive oxygen species. Indeed, impairing the DNA repair machinery by ablating xeroderma pigmentosum C restored the UVB-induced neoplastic transformation of Hif-1α-ablated keratinocytes, whereas the development of hyperkeratotic plaques was blocked by chronic antioxidant treatment. We conclude that HIF-1α plays a procarcinogenic role in UVB-induced tumorigenesis.
Identifiants
pubmed: 30878676
pii: S0022-202X(19)31329-6
doi: 10.1016/j.jid.2019.01.035
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Xpc protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2016-2028.e7Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.