15-Hydroxyprostaglandin Dehydrogenase is Downregulated and Exhibits Tumor Suppressor Activity in Gastric Cancer

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.

Keywords: :

• 15-hydroxyprostaglandin dehydrogenase
• Stomach neoplasm
• Prostaglandin E₂

ACKNOWLEDGMENTS

This study was supported by grants from the Asan Institute for Life Sciences (No. 2008-423), the National Research Foundation of Korea (No. 2007-0056398), and the KRIBB Research Initiative Program (KGM2210911). We thank Prof. Sandy D. Markowitz (Case Western Reserve University, Cleveland, OH, USA) for providing antibody reagents and for helpful discussions.

DISCLOSURE STATEMENT

No author has any competing interests.