Esophageal cancer tissues and adjacent normal mucosae in 13 patients with primary
esophageal cancer were examined for quantitative differences in
DNA-dependent protein kinase (
DNA-PK) activity and for expressions of Ku70, Ku80 and
DNA-
PKcs proteins by Western blotting and immunohistochemistry. The
tumor tissues showed higher
DNA-PK activity than the normal mucosae.
Protein levels of Ku70, Ku80 and
DNA-
PKcs correlated with
DNA-PK activities in the
tumor tissues. Immunohistochemical analysis revealed that Ku70, Ku80 and
DNA-
PKcs located predominantly in the nuclei in both the
tumor tissues and normal mucosae. In the normal epithelium, Ku70, Ku80 and
DNA-
PKcs were expressed only in the nuclei of the basal cell layers and not in those of the lumenal cell layers. In the
tumor tissues, the expressions of
DNA-PK
proteins showed intratumoral heterogeneity. The different portions in the same
tumor showed different expression levels of
DNA-PK
proteins, and even each
tumor cell showed different expression levels. These results suggest that cell differentiation and
tumor progression affect cellular
DNA-PK
protein levels and its activity. Furthermore, the intratumoral heterogeneity of
DNA-PK
protein expression in
esophageal cancer cells/ tissues also suggests the difficulty in prediction of radio- or chemo-sensitivity of the
tumor through estimation of
DNA-PK activity/
protein levels in
tumor specimens.