人乳头瘤病毒16型的E6和E7使人食管角质形成细胞永生化

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

作者信息

Sashiyama H, Shino Y, Kawamata Y, Tomita Y, Ogawa N, Shimada H, Kobayashi S, Asano T, Ochiai T, Shirasawa H

机构信息

Department of Molecular Virology, Chiba University, Inohana, School of Medicine, Chiba 260-8670, Japan.

出版信息

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

DOI:10.3892/ijo.19.1.97

PMID:11408928

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.

摘要

使用重组腺病毒将人乳头瘤病毒16型（HPV16）E6/E7转导至人食管角质形成细胞原代培养物中可延长其寿命，而未处理的细胞在14 - 16个群体倍增（PDL）内就会衰老。在寿命延长至50 - 100个PDL的食管角质形成细胞中观察到端粒酶活性上调以及获得血清抗性生长，且在100个PDL后显著增加。与具有Arg/Arg或Arg/Pro的p53多态性的其他样本不同，一个在p53第72密码子处具有Pro/Pro多态性的角质形成细胞样本对HPV16 E6/E7诱导的寿命延长和永生化具有抗性。腺病毒载体对E6/E7的高效诱导还揭示了本报告首次描述的角质形成细胞永生化的M1和M2阶段。