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Papillomavirus type 16 E6/E7 and human telomerase reverse transcriptase in esophageal cell immortalization and early transformation

In English

Författare

  • Hao Zhang
  • Yuesheng Jin
  • Xuehua Chen
  • Charlotte Jin
  • Simon Law
  • Sai-Wah Tsao
  • Yok-Lam Kwong

Summary, in English

Infection with high-risk human papillomavirus (HPV) has been implicated in the pathogenesis of esophageal squamous cell carcinoma, and up-regulation of telomerase in esophageal adenocarcinoma. We immortalized normal esophageal epithelial cells by over-expression of the HPV16 E6/E7 and human telomerase reverse transcriptase (hTERT) genes. HPV16 E6/E7-induced immortalization was accompanied by reduced RB and p53, but increased p16 and p21, protein expression. hTERT-immortalized cells had unaffected RB and p53, but significantly decreased p16 and p21, protein expression. Aurora-A protein was also upregulated in E6E7 immortalized cells, and to a less extent in hTERT immortalized cells. Fluorescence in situ hybridization showed that the Aurora-A gene locus was amplified in E6E7 immortalized cells, which might account in part for the Aurora-A overexpression. These molecular changes led to an abrogation of the G2 checkpoint. E6E7 and hTERT immortalized esophageal cells recapitulated many of the molecular changes observed in esophageal carcinomas, where RB and p53 are frequently downregulated. However, down-regulation of p16 and p21 occurred frequently in esophageal cancer, owing to aberrant gene promoter methylation. We showed in the immortalized cells that aberrant methylation had not yet set in, suggesting that promoter methylation might not be necessary for cellular immortalization. In addition to supporting the role of HPV and telomerase in esophageal carcinogenesis, our cell lines may also be useful in vitro models for further studies of esophageal carcinogenesis.

Publiceringsår

2007

Språk

Engelska

Sidor

184-194

Publikation/Tidskrift/Serie

Cancer Letters

Volym

245

Issue

1-2

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Cancer and Oncology

Nyckelord

  • esophageal cancer
  • HPV
  • telomerase

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1872-7980