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

Joo Weon Lim, Hye Young Kim, Kyung Hwan Kim

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)46093-46100
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number48
DOIs
Publication statusPublished - 2002 Nov 29

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Cell proliferation
Cyclooxygenase 2
Stomach Neoplasms
Cells
Cell Proliferation
Cell growth
Gene expression
Transfection
Stomach
DNA
Gene Expression
Dinoprostone
Indomethacin
Growth
Genes
Chemical activation
Apoptosis
Carcinogenesis
Adenocarcinoma
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Expression of Ku70 and Ku80 mediated by NF-κB and cyclooxygenase-2 is related to proliferation of human gastric cancer cells",
abstract = "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.",
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Expression of Ku70 and Ku80 mediated by NF-κB and cyclooxygenase-2 is related to proliferation of human gastric cancer cells. / Lim, Joo Weon; Kim, Hye Young; Kim, Kyung Hwan.

In: Journal of Biological Chemistry, Vol. 277, No. 48, 29.11.2002, p. 46093-46100.

Research output: Contribution to journalArticle

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