Cancer susceptibility of beta HPV49 E6 and E7 transgenic mice to 4-nitroquinoline 1-oxide treatment correlates with mutational signatures of tobacco exposure.
Virology
; 538: 53-60, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31569015
ABSTRACT
We have previously showed that a transgenic (Tg) mouse model with cytokeratin 14 promoter (K14)-driven expression of E6 and E7 from beta-3 HPV49 in the basal layer of the epidermis and of the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7 Tg mice) are highly susceptible to upper digestive tract carcinogenesis upon exposure to 4-nitroquinoline 1-oxide (4NQO). Using whole-exome sequencing, we show that in K14 HPV49 E6/E7 Tg mice, development of 4NQO-induced cancers tightly correlates with the accumulation of somatic mutations in cancer-related genes. The mutational signature in 4NQO-treated mice was similar to the signature observed in humans exposed to tobacco smoking and tobacco chewing. Similar results were obtained with K14 Tg animals expressing mucosal high-risk HPV16 E6 and E7 oncogenes. Thus, beta-3 HPV49 share some functional similarities with HPV16 in Tg animals.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nicotiana
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Proteínas Oncogênicas Virais
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Infecções por Papillomavirus
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Proteínas E7 de Papillomavirus
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Betapapillomavirus
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Neoplasias
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4-Nitroquinolina-1-Óxido
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha