Document Detail


Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer.
MedLine Citation:
PMID:  21042724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose was to study the prognostic and predictive roles of DNA protein kinase catalytic subunit (DNA-PKcs), Ku70/80 and p53 for the effect of radiotherapy in breast cancer patients. Protein expressions of Ku70/80, DNA-PKcs and p53 were examined using immunohistochemistry in tumours from 224 breast cancer patients, who were randomised to receive post-operative radiotherapy or adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil). One hundred and twenty-nine (60%) of the tumours had low expression of Ku70/80, 122 (57%) had low expression of DNA-PKcs and 65 (30%) had altered p53 expression. None of the proteins were indicative to the prognosis of local recurrence-free survival. Even though the expression of Ku70/80 and DNA-PKcs correlated well, they were not associated with treatment outcome in the same way. Low expression of Ku70/80 predicted good effect of radiotherapy (RR=0.31, 95% CI 0.13-0.76, p=0.01). In contrast, the greatest benefit of radiotherapy over chemotherapy was seen in patients with high DNA-PKcs expression (RR=0.25, 95% CI 0.07-0.84, p=0.02). Altered p53 expression predicted poor response to radiotherapy. We believe that the results reflect the different roles of DNA-PKcs and Ku70/80 in repair and cell death regulation after DNA damage. These differences could be of importance when developing drugs that target DNA repair.
Authors:
Karin Söderlund Leifler; Siv Queseth; Tommy Fornander; Marie Stenmark Askmalm
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-02-24     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1547-54     Citation Subset:  IM    
Affiliation:
Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Linköping University, Linköping, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Nuclear / metabolism*
Breast / metabolism
Breast Neoplasms / diagnosis*,  metabolism,  pathology,  radiotherapy*
Carcinoma / diagnosis*,  metabolism,  pathology,  radiotherapy*
DNA-Activated Protein Kinase / metabolism*
DNA-Binding Proteins / metabolism*
Disease Progression
Disease-Free Survival
Down-Regulation
Female
Humans
Immunohistochemistry
Nuclear Proteins / metabolism*
Prognosis
Randomized Controlled Trials as Topic
Tissue Array Analysis
Treatment Outcome
Tumor Suppressor Protein p53 / metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; 0/Nuclear Proteins; 0/Tumor Suppressor Protein p53; EC 2.7.11.1/DNA-Activated Protein Kinase; EC 2.7.11.1/PRKDC protein, human

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