15-hydroxyprostaglandin dehydrogenase is downregulated and exhibits tumor suppressor activity in gastric cancer

Cancer Invest. 2011 May;29(4):257-65. doi: 10.3109/07357907.2011.568562.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / enzymology*
  • Adenoma / genetics
  • Adenoma / pathology
  • Apoptosis
  • Carcinoma / enzymology*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Dinoprostone / metabolism
  • Down-Regulation
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Gastritis / enzymology*
  • Gastritis / genetics
  • Gastritis / pathology
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Metaplasia
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Precancerous Conditions / enzymology*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Time Factors
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Tumor Suppressor Proteins
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • EGFR protein, human
  • ErbB Receptors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Dinoprostone