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.
- BCC, basal cell carcinoma
- DSB, double-strand break
- EMSA, electrophoretic mobility shift assay
- IHC, immunohistochemical
- NHEJ, non-homologous end joining
- NMSC, non-melanoma skin cancer
- SCC, squamous cell carcinoma
- TBS, TRIS-buffered saline
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↵* Present affiliation: University of Rome “Tor Vergata”, Rome, Italy.
Published Online First 23 February 2006
Competing interests: None declared.
P Parrella and P Mazzarelli contributed equally to this work.