Document Detail


An accelerated senescence response to radiation in wild-type p53 glioblastoma multiforme cells.
MedLine Citation:
PMID:  16871885     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Radiotherapy is one of the few treatment options available for glioblastoma multiforme (GBM); however, the basis for its overall ineffectiveness in GBM is not fully understood. The present study was designed to explore the nature of the response to ionizing radiation in GBM cells to gain insight into the basis for the general failure of radiotherapy in the treatment of this disease. METHODS: The response to fractionated radiotherapy was examined in GBM cell lines with differing p53 status. A viable cell number was determined during an 8-day period; accelerated senescence was based on beta-galactosidase staining and cell morphology; apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and fluorescence-activated cell-sorter analysis, whereas the expression of cell-cycle regulatory proteins was monitored by Western blot analysis. Based on clonogenic survival, the wild-type p53 U87 cells and mutant p53 T98 cells demonstrated essentially identical sensitivity to fractionated radiotherapy; however, neither cell line underwent apoptosis, and the primary response to irradiation was growth arrest. The wild-type p53 GBM cells showed clear evidence of accelerated senescence in response to irradiation. In contrast, senescence was not evident in mutant p53 GBM cells or GBM cells in which p53 function was abrogated by the viral E6 protein. The T98 (mutant p53) cells demonstrated a relatively robust proliferative recovery whereas both the rate and extent of recovery were attenuated in the wild-type p53 U87 cells. CONCLUSIONS: Both accelerated senescence and conventional growth arrest are likely to represent alternative responses to apoptosis in irradiated GBM cells.
Authors:
Quincy A Quick; David A Gewirtz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  105     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-28     Completed Date:  2006-09-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / radiation effects
Cell Aging / radiation effects*
Cell Cycle Proteins / metabolism
Cell Line, Tumor / radiation effects
Cell Proliferation / radiation effects
Dose Fractionation
Glioblastoma / metabolism,  pathology*,  radiotherapy*
Humans
Recovery of Function / radiation effects
Tumor Suppressor Protein p53 / physiology*
Grant Support
ID/Acronym/Agency:
T32 CA085159/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Tumor Suppressor Protein p53

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