| Abrogation of radiation-inducible telomerase upregulation in HPV16 E6 transfectants of human lymphoblasts. | |
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MedLine Citation:
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PMID: 14704845 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Telomerase activity in a human lymphoblastoid cell line with wild-type p53 status (TK6) was previously shown to be rapidly induced by ionizing radiation doses as low as 10 cGy. Since this low-dose response was absent in a closely related cell line overexpressing a mutant form of p53 (WTK1), the putative involvement of p53 was further investigated using stable human papillomavirus 16 (HPV16) E6 transfectants of these cell lines. The E6 product mediates rapid degradation of wild-type p53, but has also been found to upregulate telomerase. MATERIAL AND METHODS: Telomerase activity in HPV16 E6 transfectants of the human lymphoblastoid cell lines TK6 and WTK1 was measured by PCR/ELISA and was quantified using internal standards (titration by cell number) run within each separate assay. Mean telomere length was determined by Southern hybridization of terminal restriction fragments with a biotin-labeled telomeric DNA probe. RESULTS: The TK6E6 and the WTK1E6 cells exhibited higher baseline telomerase activities than the parental cells. This was also accompanied by increased telomere lengths. Radiation exposure (up to 10 Gy) was unable to significantly further enhance telomerase activities, although the dynamic range of the assay would have allowed to record higher signals. CONCLUSION: The lacking radiation induction of telomerase activities in the E6 transfectants could reflect saturation, if E6 and radiation would share a common pathway of telomerase upregulation. Present evidence from the literature, however, suggests that E6 mediates telomerase reverse transcriptase (TERT) subunit transcriptional activation, whereas radiation signals to posttranscriptional/posttranslational control of telomerase activity. Therefore, the present data enforce the previous hypothesis of a p53 dependence of telomerase upregulation by low doses of radiation and its abrogation, likely due to p53 degradation, in E6-expressing cells. |
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Authors:
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Dirk Neuhof; Frédérique Auberger; Alexandra Ruess; Frederik Wenz; Klaus-Josef Weber |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al] Volume: 180 ISSN: 0179-7158 ISO Abbreviation: Strahlenther Onkol Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2004-01-05 Completed Date: 2004-02-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8603469 Medline TA: Strahlenther Onkol Country: Germany |
Other Details:
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Languages: eng Pagination: 52-6 Citation Subset: IM |
Affiliation:
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Radiobiology Research Laboratory, Department of Clinical Radiology, University of Heidelberg, Germany. dirk_neuhof@med.uni-heidelberg.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Transformed Cell Transformation, Neoplastic / genetics* Dose-Response Relationship, Radiation Enzyme Induction / radiation effects Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Enzymologic / radiation effects* Humans Lymphocytes Neoplasms, Radiation-Induced / enzymology, genetics* Oncogene Proteins, Viral / genetics* Polymerase Chain Reaction Repressor Proteins* Telomerase / biosynthesis, genetics* Transfection* Tumor Suppressor Protein p53 / genetics* Up-Regulation / radiation effects |
| Chemical | |
Reg. No./Substance:
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0/E6 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; EC 2.7.7.49/Telomerase |
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