title: Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): a natural disease model provides insights into viral carcinogenesis.
abstract: Uncertainty regarding the causality of human papillomaviruses (HPVs) in squamous cell carcinoma of the head and neck (SCCHN) necessitates better in vitro models. We carried out molecular analyses of a novel, naturally HPV-16-transformed SCCHN cell line (UPCI:SCC090) and show high copy number of HPV-16 DNA, present in a head to tail, tandemly repeated integrated state. Sequence analysis of the HPV-16 long control region (LCR) in UPCI:SCC090 revealed a deletion of 163 bp, removing a portion of the enhancer sequence, including the binding sites for the transcription factors YY1 and NF1. The E6 and E7 oncogenes of HPV-16 are expressed at high levels in this cell lines, as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). UPCI:SCC090 contains wild-type tumour suppressor TP53 gene, and undetectable p53 protein, except after treatment with cisplatin, specific proteasome inhibitors or by E6 RNA interference, suggesting E6-dependent degradation of p53 in this cell line. The results of our studies are consistent with a causative role of HPV-16 in the pathogenesis of SCCHN.
authors.affiliation: UPCI Research Pavilion, The Hillman Cancer Center, 5117 Centre Avenue, Room 1.19d, Pittsburgh, PA 15213-1863, USA. ferrisrl@upmc.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: Ivan
authors.initials: I
authors.lastname: Martinez
authors.forename: Nicky
authors.initials: N
authors.lastname: Sirianni
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Andrés
authors.initials: A
authors.lastname: López-Albaitero
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Gollin
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Johnson
authors.forename: Saleem
authors.initials: S
authors.lastname: Khan
mesh_terms: D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000821:virology*; D006801:Humans; D008954:Models, Biological; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53