title: The human papillomavirus 16 European-T350G E6 variant can immortalize but not transform keratinocytes in the absence of E7.
abstract: Human papillomavirus type 16 is commonly implicated in HPV-related cancers. However, only a small number of infected individuals progress to this stage. Epidemiological evidence demonstrated that oncogenic risk is population-specific and variations within the viral oncogene, E6, have been suggested to play a role in these findings. Of focus in this study is the European-T350G variant, which is characterized by an L>V amino acid substitution at residue 83 of the prototype E6 protein. To elucidate the functional effects of this polymorphism, we followed keratinocytes transduced with E-T350G E6 for over 60 passages and compared them to keratinocytes transduced, in parallel, with prototype or Asian-American (Q14H/L83V/H78Y) E6. We found that although E-T350G E6 immortalized transduced keratinocytes in the absence of E7, these cells were not fully transformed. We also found that E-T350G down-regulated E-cadherin compared to the other variants, providing a possible link between its population-based oncogenicity and host genetic variations.
authors: Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada; Biotechnology Program, Lakehead University, Thunder Bay, ON, Canada.
authors: Melissa
authors: M
authors: Togtema
authors: Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada; Biotechnology Program, Lakehead University, Thunder Bay, ON, Canada.
authors: Robert
authors: R
authors: Jackson
authors: Regional Cancer Care, Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada.
authors: Christina
authors: C
authors: Richard
authors: Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada; Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
authors: Sarah
authors: S
authors: Niccoli
authors: Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada; Department of Biology, Lakehead University, Thunder Bay, ON, Canada. Electronic address: zehbei@tbh.net.
authors: Ingeborg
authors: I
authors: Zehbe
mesh_terms: D015415:Biomarkers; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D015870:Gene Expression; D014644:Genetic Variation; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D015415:Biomarkers; D015820:Cadherins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: E-T350G; E-cadherin; E6 protein; HPV16 variant; Human papillomavirus; Immortalization; Transformation