The human papillomavirus 16 European-T350G E6 variant can immortalize but not transform keratinocytes in the absence of E7

  • Togtema M
  • Jackson R
  • Richard C
 et al. 
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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.

Author-supplied keywords

  • E-T350G
  • E-cadherin
  • E6 protein
  • HPV16 variant
  • Human papillomavirus
  • Immortalization
  • Transformation

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Authors

  • Melissa Togtema

  • Robert Jackson

  • Christina Richard

  • Sarah Niccoli

  • Ingeborg Zehbe

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