An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma.
Cell Rep
; 29(6): 1660-1674.e7, 2019 11 05.
Article
en En
| MEDLINE
| ID: mdl-31693903
ABSTRACT
The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Neoplasias Orofaríngeas
/
Proteínas Oncogénicas Virales
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Modelos Animales de Enfermedad
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Proteínas E7 de Papillomavirus
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Carcinoma de Células Escamosas de Cabeza y Cuello
/
Neoplasias de Cabeza y Cuello
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos