title: Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice.
abstract: High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Avenue, Madison, WI 53706, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Jabbar
authors.forename: Katerina
authors.initials: K
authors.lastname: Strati
authors.forename: Myeong Kyun
authors.initials: MK
authors.lastname: Shin
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000139:chemically induced* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D012097:Repressor Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology
chemical_list: D002273:Carcinogens; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D037521:Virulence Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D015112:4-Nitroquinoline-1-oxide
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