C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis

Virus Res. 2018 Mar 2:247:94-101. doi: 10.1016/j.virusres.2018.02.009. Epub 2018 Feb 13.

Abstract

The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells. Transfection with the E6^E7-GFP or E7-GFP construct had no effect on the number of the apoptotic cells, compared with control cells. Conversely, transfection with the E6*II construct resulted in higher cell death than the control cells. Taken together, these results suggested that E6*I or E6*II, the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis, when transfected in C-33A cells.

Keywords: Apoptosis resistance; Cisplatin; E6 splice donor mutant; E6 spliced forms; HPV16 E6; Transfected C-33A cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cervix Uteri / drug effects
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Cisplatin / pharmacology*
  • Female
  • Gene Expression
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / metabolism
  • Humans
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Antineoplastic Agents
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Green Fluorescent Proteins
  • Cisplatin