Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

Virology. 2016 Sep:496:1-8. doi: 10.1016/j.virol.2016.05.017. Epub 2016 May 26.

Abstract

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC.

Keywords: E6; E7; Feline SCC; Feline oncology; Felis catus papillomavirus; Oncogenic viruses; Veterinary medicine; Veterinary virology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / etiology*
  • Carrier Proteins
  • Cats
  • Cell Line
  • Gene Expression Regulation, Viral*
  • Mice
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism*
  • Papillomaviridae / physiology*
  • Papillomavirus E7 Proteins / genetics*
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / veterinary
  • Protein Binding
  • RNA, Messenger / genetics
  • Signal Transduction
  • Transcriptional Activation*

Substances

  • Carrier Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Messenger