Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer

• Published in: Journal of clinical pathology Vol. 59; no. 11; pp. 1181 - 1185
• Main Authors: Parrella, P, Mazzarelli, P, Signori, E, Perrone, G, Marangi, G F, Rabitti, C, Delfino, M, Prencipe, M, Gallo, A P, Rinaldi, M, Fabbrocini, G, Delfino, S, Persichetti, P, Fazio, V M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01-11-2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Antigens, Nuclear - metabolism; basal cell carcinoma; BCC; Biological and medical sciences; Biomarkers, Tumor - metabolism; Carcinoma, Basal Cell - metabolism; Carcinoma, Basal Cell - pathology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Proliferation; Dermatology; Disease Progression; DNA-Binding Proteins - metabolism; double-strand break; DSB; Electrophoretic Mobility Shift Assay; EMSA; Humans; IHC; immunohistochemical; Investigative techniques, diagnostic techniques (general aspects); Ki-67 Antigen - metabolism; Ku Autoantigen; Medical sciences; Neoplasm Proteins - metabolism; NHEJ; NMSC; non-homologous end joining; non-melanoma skin cancer; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; SCC; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; squamous cell carcinoma; TBS; TRIS-buffered saline; Tumors of the skin and soft tissue. Premalignant lesions; Up-Regulation; Human; Binding; Skin disease; Anatomic pathology; Malignant melanoma; Malignant tumor; Heterodimer; Biological activity; Skin cancer
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2005.031088

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.