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DC Field | Value | Language |
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dc.contributor.author | Steenbergen, RD | - |
dc.contributor.author | Kramer, D | - |
dc.contributor.author | Meijer, CJ | - |
dc.contributor.author | Walboomers, JM | - |
dc.contributor.author | Trott, DA | - |
dc.contributor.author | Cuthbert, AP | - |
dc.contributor.author | Newbold, RF | - |
dc.contributor.author | Overkamp, WJ | - |
dc.contributor.author | Zdzienicka, MZ | - |
dc.contributor.author | Snijders, PJ | - |
dc.coverage.spatial | 8 | en |
dc.date.accessioned | 2009-03-27T10:39:14Z | - |
dc.date.available | 2009-03-27T10:39:14Z | - |
dc.date.issued | 2001 | - |
dc.identifier.citation | Journal of the National Cancer Institute. 93 (11) 865-872 | en |
dc.identifier.issn | 0027-8874 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/3180 | - |
dc.description.abstract | BACKGROUND: High-risk human papillomavirus (HPV) types play a major role in the development of cervical cancer in vivo and can induce immortalization of primary human keratinocytes in vitro. Activation of the telomere-lengthening enzyme telomerase constitutes a key event in both processes. Because losses of alleles from chromosome 6 and increased telomerase activity have been observed in high-grade premalignant cervical lesions, we analyzed whether human chromosome 6 harbors a putative telomerase repressor locus that may be involved in HPV-mediated immortalization. METHODS: Microcell-mediated chromosome transfer was used to introduce chromosomes 6 and 11 to the in vitro generated HPV type 16 (HPV16)-immortalized keratinocyte cell line FK16A and to the in vivo derived HPV16-containing cervical cancer cell line SIHA: Hybrid clones were analyzed for growth characteristics, telomerase activity, human telomerase reverse transcriptase (hTERT) and HPV16 E6 expression, and telomere length. FK16A hybrid clones were also transduced with an hTERT-containing retrovirus to examine the effect of ectopic hTERT expression on growth. Statistical tests were two-sided. RESULTS: Introduction of human chromosome 6 but not of chromosome 11 to both cell lines yielded hybrid cells that demonstrated crisis-like features (i.e., enlarged and flattened morphology, vacuolation, and multinucleation) and underwent growth arrest after a marked lag period. In the chromosome 6 hybrid clones analyzed, telomerase activity and hTERT messenger RNA (mRNA) expression were statistically significantly reduced compared with those in the chromosome 11 hybrid clones (for telomerase activity, P =.004 for the FK16A hybrids and P =.039 for the SiHa hybrids; for hTERT mRNA expression, P =.003 for the FK16A hybrids). The observed growth arrest was associated with telomeric shortening. Ectopic expression of hTERT in FK16A cells could prevent the telomeric shortening-based growth arrest induced by chromosome 6. CONCLUSIONS: Chromosome 6 may harbor a repressor of hTERT transcription, the loss of which may be involved in HPV-mediated immortalization. | en |
dc.format.extent | 766412 bytes | - |
dc.format.mimetype | application/txt | - |
dc.language.iso | en | - |
dc.publisher | Oxford University Press | en |
dc.subject | Cell Division | en |
dc.subject | Cell Line, Transformed | en |
dc.subject | Chromosomes, Human, Pair 11 | en |
dc.subject | Chromosomes, Human, Pair 6 | en |
dc.subject | DNA-Binding Proteins | en |
dc.subject | Female | en |
dc.subject | Genes, Reporter | en |
dc.subject | Humans | en |
dc.subject | Hybrid Cells | en |
dc.subject | Keratinocytes | en |
dc.title | Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line | en |
dc.type | Research Paper | en |
Appears in Collections: | Community Health and Public Health Dept of Health Sciences Research Papers |
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File | Description | Size | Format | |
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Embargoed Paper.txt | 204 B | Text | View/Open |
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