Expression of Ku70 and Ku80 mediated by NF-κB and cyclooxygenase-2 is related to proliferation of human gastric cancer cells

Cyclooxygenase-2 (COX-2) expression is mediated by constitutive NF-κB and regulates human gastric cancer cell growth and proliferation. Inactivating Ku70 or Ku80 suppresses cell growth and induces apoptosis. It has been hypothesized that Ku70 and Ku80 expression may be associated with NF-κB activation and COX-2 expression and is involved in cell proliferation. In this study, we found that inhibition of constitutive NF-κB (by transfecting a mutated IκBα gene) and of COX-2 (by treatment with indomethacin and NS-398) suppressed Ku70 and Ku80 expression in cells. Treatment with prostaglandin E₂ adenocarcinoma gastric (AGS) increased expression of these Ku proteins in cells with low constitutive NF-κB levels. Inhibition of the Ku DNA end-binding activity by transfection with the C-terminal Ku80 expression gene suppressed cell proliferation. Ku70 or Ku80 overexpression by transfection with the Ku70 or Ku80 expression gene, respectively, enhanced proliferation of cells with low NF-κB levels. These results demonstrate that Ku70 and Ku80 expression is mediated by constitutively activated NF-κB and constitutively expressed COX-2 in gastric cancer cells and that the high Ku DNA end-binding activity contributes to cell proliferation. Ku70 and Ku80 expression may be related to gastric cell proliferation and carcinogenesis.