Abstract
We investigated the tumor suppressor activity and regulatory mechanism of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer; 15-PGDH expression was lost in 70.1% of malignant human gastric tissues, but was preserved in normal and metaplastic gastritis. KATO III and SNU-719 cells were transfected with pcDNA3.1-empty vector or an expression vector encoding wild-type 15-PGDH. In TUNEL assays apoptotic cell numbers were increased in KATO-PGDH-WT cells compared with control. We found that EGFR and ERK1/2 inhibitors clearly increased the expression of 15-PGDH in KATO III cells. Our findings demonstrate both downregulation and a tumor suppressor activity of 15-PGDH in gastric cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoma / enzymology*
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Adenoma / genetics
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Adenoma / pathology
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Apoptosis
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Carcinoma / enzymology*
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Carcinoma / genetics
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Carcinoma / pathology
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Cell Line, Tumor
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Cell Proliferation
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Dinoprostone / metabolism
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Down-Regulation
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism
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Gastritis / enzymology*
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Gastritis / genetics
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Gastritis / pathology
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Humans
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Hydroxyprostaglandin Dehydrogenases / genetics
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Hydroxyprostaglandin Dehydrogenases / metabolism*
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Immunohistochemistry
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In Situ Nick-End Labeling
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Metaplasia
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Precancerous Conditions / enzymology*
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Precancerous Conditions / genetics
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Precancerous Conditions / pathology
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Protein Kinase Inhibitors / pharmacology
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Stomach Neoplasms / enzymology*
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology
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Time Factors
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Transfection
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Protein Kinase Inhibitors
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Tumor Suppressor Proteins
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Hydroxyprostaglandin Dehydrogenases
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15-hydroxyprostaglandin dehydrogenase
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EGFR protein, human
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ErbB Receptors
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Dinoprostone