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Restoration of Telomeres in Human Papillomavirus-Immortalized Human Anogenital Epithelial Cells

Klingelhutz, A J, Barber, S A, Smith, P P, Dyer, K, McDougall, J K·1994·Molecular and Cellular Biology
DOI 10.1128/mcb.14.2.961
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Abstract

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

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Cited by

Metadata

Authors
Klingelhutz, A. J., Barber, S. A., Smith, P. P., Dyer, K., & McDougall, J. K.
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
1994-02
Volume
14
Issue
2
Pages
961-969
ISSN
  • 0270-7306
  • 1098-5549
DOI
10.1128/mcb.14.2.961
Cited by
86
References
9
Language
en

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