Decreased expression of DNA-dependent protein kinase, a DNA repair protein, during human colon carcinogenesis.
DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and the Ku70 and Ku86 proteins, participates in the repair of DNA double-strand breaks (DSBs). We assessed its expression immunohistochemically in normal human colon tissue, colon adenomas, colon carcinomas, and normal tissue distant from carcinomas. Normal colonocytes expressed all DNA-PK proteins. Compared with the expression in normal tissue [176.62 +/- 18.56 (the intensity of expression x the percentage of cells expressing this protein), mean + SE], the expression of Ku70 was significantly reduced in adenomas (36.62 +/- 11.09; P < 0.001) and carcinomas (85.68 +/- 15.76; P < 0.01), as was the expression of Ku86 [(113.10 +/- 10.22 versus 41.66 +/- 14.71 in adenomas (P < 0.01) or versus 85.68 +/- 15.76 in carcinomas (P < 0.05)]. The expression of DNA-PKcs was not significantly changed. The marked underexpression of Ku70 and Ku86 starting at the adenoma stage may be crucial to the development of colon cancer.
Rigas
B
B
American Health Foundation, Valhalla, New York 10595, USA.
Borgo
S
S
Elhosseiny
A
A
Balatsos
V
V
Manika
Z
Z
Shinya
H
H
Kurihara
N
N
Go
M
M
Lipkin
M
M
D000236:Adenoma / Q000201:enzymology; D000368:Aged; D034961:Antigens, Nuclear; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology*; D004265:DNA Helicases; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen