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

Transduction of human papillomavirus type 16 (HPV16) E6/E7 into primary cul ture of human esophageal keratinocytes using a recombinant adenovirus prolo nged the life-span, while untreated cells senesced within 14-16 population doublings (PDLs). Up-regulation of telomerase activity and acquisition of s erum-resistant growth were observed in the esophageal keratinocytes with ex tended lifespan between 50 and 100 PDLs, and drastically increased after 10 0 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 immor talization, 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 ve ctor also revealed the M1 and M2 stages of keratinocyte immortalization fir st described in this report.