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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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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
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author 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.
author_facet 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.
author_sort Carper, Miranda B.
collection PubMed
description 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.
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spelling pubmed-68709172019-11-21 An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma 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. Cell Rep Article 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. 2019-11-05 /pmc/articles/PMC6870917/ /pubmed/31693903 http://dx.doi.org/10.1016/j.celrep.2019.10.005 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
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.
An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title_full An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title_fullStr An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title_full_unstemmed An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title_short An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma
title_sort immunocompetent mouse model of hpv16(+) head and neck squamous cell carcinoma
topic Article
url 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
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