Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer.
BACKGROUND
Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks.


OBJECTIVE
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.
Oncology Research Laboratory, IRCCS Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
P
P
Parrella
P
P
Mazzarelli
E
E
Signori
G
G
Perrone
G F
GF
Marangi
C
C
Rabitti
M
M
Delfino
M
M
Prencipe
A P
AP
Gallo
M
M
Rinaldi
G
G
Fabbrocini
S
S
Delfino
P
P
Persichetti
V M
VM
Fazio
D034961:Antigens, Nuclear / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D000072200:Ku Autoantigen; D009363:Neoplasm Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen