Human Papillomavirus E6 Knockdown Restores Adenovirus Mediated-estrogen Response Element Linked p53 Gene Transfer in HeLa Cells

  • Kajitani, Koji (Department of Obstetrics and Gynecology, Osaka City General Hospital) ;
  • Ken-Ichi, Honda (Department of Obstetrics and Gynecology, Kashiwara Municipal Hospital) ;
  • Terada, Hiroyuki (Department of Obstetrics and Gynecology, Kashiwara Municipal Hospital) ;
  • Yasui, Tomoyo (Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine) ;
  • Sumi, Toshiyuki (Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine) ;
  • Koyama, Masayasu (Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine) ;
  • Ishiko, Osamu (Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine)
  • Published : 2016.01.11


The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor ${\beta}$, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower ${\beta}$-tubulin levels and comparatively higher p53/${\beta}$-tubulin or CAR/${\beta}$-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.


Adenovirus mediated transduction;codon 72 polymorphism;p53;siRNA


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