Document Detail

Radiosensitization of oropharyngeal squamous cell carcinoma cells by human papillomavirus 16 oncoprotein e6∗i.
MedLine Citation:
PMID:  21106305     Owner:  NLM     Status:  In-Data-Review    
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.
Ervinna Pang; Naomi C Delic; Angela Hong; Mei Zhang; Barbara R Rose; J Guy Lyons
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Publication Detail:
Type:  Journal Article     Date:  2010-11-23
Journal Detail:
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:
Created Date:  2011-02-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  860-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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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