Journal article
Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells
Molecular and cellular biology, Vol.14(2), pp.961-969
02/1994
DOI: 10.1128/mcb.14.2.961-969.1994
PMCID: PMC358451
PMID: 8289836
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.
Details
- Title: Subtitle
- Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells
- Creators
- Aloysius J Klingelhutz - Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104Sheila A Barber - Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104Patricia P Smith - Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104Karen Dyer - Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104James K McDougall - Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.14(2), pp.961-969
- DOI
- 10.1128/mcb.14.2.961-969.1994
- PMID
- 8289836
- PMCID
- PMC358451
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 02/1994
- Academic Unit
- Microbiology and Immunology; Radiation Oncology
- Record Identifier
- 9984002387502771
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