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An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

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-...

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Detalles Bibliográficos
Autores principales: Carper, Miranda B., Troutman, Scott, Wagner, Bethany L., Byrd, Kevin M., Selitsky, Sara R., Parag-Sharma, Kshitij, Henry, Erin C., Li, Weimin, Parker, Joel S., Montgomery, Stephanie A., Cleveland, John L., Williams, Scott E., Kissil, Joseph L., Hayes, David N., Amelio, Antonio L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870917/
https://www.ncbi.nlm.nih.gov/pubmed/31693903
http://dx.doi.org/10.1016/j.celrep.2019.10.005
Descripción
Sumario: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 PIK3CA(E545K) 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 immuno- suppression.