Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium.
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.
Tonotsuka
Norio
N
Department of Radiation Research, Faculty of Medicine, Tohoku University, Sendai 980-8575, Japan.
Hosoi
Yoshio
Y
Miyazaki
Shukichi
S
Miyata
Go
G
Sugawara
Ko
K
Mori
Takahiro
T
Ouchi
Noriaki
N
Satomi
Susumu
S
Matsumoto
Yoshihisa
Y
Nakagawa
Keiichi
K
Miyagawa
Kiyoshi
K
Ono
Tetsuya
T
D002478:Cells, Cultured; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000201:enzymology*; D004947:Esophagus / Q000201:enzymology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D013223:Statistics as Topic
D051747:DNA-Activated Protein Kinase