Immortalization of human esophageal keratinocytes by E6 and E7 of human papillomavirus type 16

Int J Oncol. 2001 Jul;19(1):97-103. doi: 10.3892/ijo.19.1.97.

Abstract

Transduction of human papillomavirus type 16 (HPV16) E6/E7 into primary culture of human esophageal keratinocytes using a recombinant adenovirus prolonged the life-span, while untreated cells senesced within 14-16 population doublings (PDLs). Up-regulation of telomerase activity and acquisition of serum-resistant growth were observed in the esophageal keratinocytes with extended life-span between 50 and 100 PDLs, and drastically increased after 100 PDLs. A keratinocyte sample with a polymorphism of Pro/Pro at codon 72 of p53 showed resistance to HPV16 E6/E7-induced life-span-extension and immortalization, in contrast to others with p53 polymorphisms of Arg/Arg or Arg/Pro, which did not. The high efficiency of E6/E7-induction by adenovirus vector also revealed the M1 and M2 stages of keratinocyte immortalization first described in this report.

MeSH terms

  • Adenoviridae / genetics
  • Calcium / pharmacology
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Cell Transformation, Viral
  • Colony-Forming Units Assay
  • DNA Primers / chemistry
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology*
  • Esophagus / metabolism
  • Esophagus / virology*
  • Genetic Vectors
  • Humans
  • In Situ Hybridization
  • In Vitro Techniques
  • Keratins / metabolism
  • Microscopy, Phase-Contrast
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / genetics*
  • Papillomavirus E7 Proteins
  • Repressor Proteins*
  • Telomere / metabolism
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • DNA Primers
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • oncogene protein E7, Human papillomavirus type 16
  • Keratins
  • Calcium