Document Detail

Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer.
MedLine Citation:
PMID:  16497868     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks.
AIM: To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas.
METHODS: Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70-Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls.
RESULTS: A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins.
CONCLUSIONS: Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.
P Parrella; P Mazzarelli; E Signori; G Perrone; G F Marangi; C Rabitti; M Delfino; M Prencipe; A P Gallo; M Rinaldi; G Fabbrocini; S Delfino; P Persichetti; V M Fazio
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2006-02-23
Journal Detail:
Title:  Journal of clinical pathology     Volume:  59     ISSN:  0021-9746     ISO Abbreviation:  J. Clin. Pathol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-30     Completed Date:  2006-11-30     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0376601     Medline TA:  J Clin Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1181-5     Citation Subset:  AIM; IM    
Oncology Research Laboratory, IRCCS Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
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MeSH Terms
Antigens, Nuclear / metabolism*
Carcinoma, Basal Cell / metabolism*,  pathology
Carcinoma, Squamous Cell / metabolism*,  pathology
Cell Proliferation
DNA-Binding Proteins / metabolism*
Disease Progression
Electrophoretic Mobility Shift Assay
Ki-67 Antigen / metabolism
Neoplasm Proteins / metabolism
Skin Neoplasms / metabolism*,  pathology
Tumor Markers, Biological / metabolism
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ki-67 Antigen; 0/Ku autoantigen; 0/Neoplasm Proteins; 0/Tumor Markers, Biological

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