Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential
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- Masahiko Tsujii
- Departments of Medicine and Cell Biology, Molecular Toxicology Center, Vanderbilt University Medical Center and the Veterans Affairs Medical Center, Nashville, TN 37232; and First Department of Medicine, Osaka University School of Medicine, Osaka, Japan
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- Sunao Kawano
- Departments of Medicine and Cell Biology, Molecular Toxicology Center, Vanderbilt University Medical Center and the Veterans Affairs Medical Center, Nashville, TN 37232; and First Department of Medicine, Osaka University School of Medicine, Osaka, Japan
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- Raymond N. DuBois
- Departments of Medicine and Cell Biology, Molecular Toxicology Center, Vanderbilt University Medical Center and the Veterans Affairs Medical Center, Nashville, TN 37232; and First Department of Medicine, Osaka University School of Medicine, Osaka, Japan
抄録
<jats:p>Recent epidemiologic studies have shown a 40–50% reduction in mortality from colorectal cancer in individuals who take nonsteroidal antiinflammatory drugs on a regular basis compared with those not taking these agents. One property shared by all of these drugs is their ability to inhibit cyclooxygenase (COX), a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. Human colon cancer cells (Caco-2) were permanently transfected with a COX-2 expression vector or the identical vector lacking the COX-2 insert. The Caco-2 cells, which constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. Biochemical changes associated with this phenotypic change included activation of metalloproteinase-2 and increased RNA levels for the membrane-type metalloproteinase. Increased invasiveness and prostaglandin production were reversed by treatment with sulindac sulfide, a known COX inhibitor. These studies demonstrate that constitutive expression of COX-2 can lead to phenotypic changes that alter the metastatic potential of colorectal cancer cells.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 94 (7), 3336-3340, 1997-04
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1361981471009968000
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- NII論文ID
- 80009595253
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- ISSN
- 10916490
- 00278424
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