PT  - JOURNAL ARTICLE
AU  - P Parrella
AU  - P Mazzarelli
AU  - E Signori
AU  - G Perrone
AU  - G F Marangi
AU  - C Rabitti
AU  - M Delfino
AU  - M Prencipe
AU  - A P Gallo
AU  - M Rinaldi
AU  - G Fabbrocini
AU  - S Delfino
AU  - P Persichetti
AU  - V M Fazio
TI  - Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer
AID  - 10.1136/jcp.2005.031088
DP  - 2006 Nov 01
TA  - Journal of Clinical Pathology
PG  - 1181--1185
VI  - 59
IP  - 11
4099  - http://jcp.bmj.com/content/59/11/1181.short
4100  - http://jcp.bmj.com/content/59/11/1181.full
SO  - J Clin Pathol2006 Nov 01; 59
AB  - 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.