| Radiosensitization of oropharyngeal squamous cell carcinoma cells by human papillomavirus 16 oncoprotein e6∗i. | |
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MedLine Citation:
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PMID: 21106305 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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PURPOSE: Patients with oropharyngeal squamous cell carcinoma (OSCC) whose disease is associated with high-risk human papillomavirus (HPV) infection have a significantly better outcome than those with HPV-negative disease, but the reasons for the better outcome are not known. We postulated that they might relate to an ability of HPV proteins to confer a better response to radiotherapy, a commonly used treatment for OSCC. METHODS AND MATERIALS: We stably expressed the specific splicing-derived isoforms, E6∗I and E6∗II, or the entire E6 open reading frame (E6total), which gives rise to both full length and E6∗I isoforms, in OSCC cell lines. Radiation resistance was measured in clonogenicity assays, p53 activity was measured using transfected reporter genes, and flow cytometry was used to analyze cell cycle and apoptosis. RESULTS: E6∗I and E6total sensitized the OSCC cells to irradiation, E6∗I giving the greatest degree of radiosensitization (approximately eightfold lower surviving cell fraction at 10 Gy), whereas E6∗II had no effect. In contrast to radiosensitivity, E6∗I was a weaker inhibitor than E6total of tumor suppressor p53 transactivator activity in the same cells. Flow cytometric analyses showed that irradiated E6∗I expressing cells had a much higher G2M:G1 ratio than control cells, indicating that, after G2, cells were diverted from the cell cycle to programmed cell death. CONCLUSION: This study supports a role for E6∗I in the enhanced responsiveness of HPV-positive oropharyngeal carcinomas to p53-independent radiation-induced death. |
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Authors:
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Ervinna Pang; Naomi C Delic; Angela Hong; Mei Zhang; Barbara R Rose; J Guy Lyons |
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Publication Detail:
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Type: Journal Article Date: 2010-11-23 |
Journal Detail:
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Title: International journal of radiation oncology, biology, physics Volume: 79 ISSN: 1879-355X ISO Abbreviation: Int. J. Radiat. Oncol. Biol. Phys. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603616 Medline TA: Int J Radiat Oncol Biol Phys Country: United States |
Other Details:
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Languages: eng Pagination: 860-5 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, NSW, Australia; Discipline of Infectious Diseases and Immunology, University of Sydney, NSW, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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