Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress.
J Invest Dermatol
; 139(9): 2016-2028.e7, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30878676
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
/
Radiacao_solar
/
Tipos_de_cancer
/
Pele
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Raios Ultravioleta
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Ceratose Actínica
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Carcinogênese
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
França