Yonsei Med J.  2008 Dec;49(6):917-922. 10.3349/ymj.2008.49.6.917.

Decreased Expression of 15-hydroxyprostaglandin Dehydrogenase in Gastric Carcinomas

• Jang TJ
• Ji YS
• Jung KH

• KMID: 1782939
• DOI: http://doi.org/10.3349/ymj.2008.49.6.917

Abstract

PURPOSE
Gastric carcinoma tissues release high level of prostaglandin E2 (PGE2) when compared to non-neoplastic mucosa, and cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in prostaglandin (PG) biosynthesis, is often overexpressed in gastric carcinomas and during gastric carcinogenesis. However, little is known about the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for the biological inactivation of PG, in gastric carcinomas. MATERIALS AND METHODS: We investigated the expression of 15-PGDH in 28 cases of advanced gastric carcinomas by Western blot analysis and also the relation between its expression and the gene promoter methylation. RESULTS: 15-PGDH expression was significantly decreased in gastric carcinomas compared to corresponding non-neoplastic tissues and inversely correlated with the expression of proliferating cell nuclear antigen in gastric carcinomas. However, there was no correlation between 15-PGDH expression and pathological findings such as nodal metastasis and vascular invasion. Promoter hypermethylation of 15-PGDH gene was not detected in carcinomas, with only a negligible expression of the enzyme. CONCLUSION: Our results suggested that 15-PGDH has tumor suppressor activity in gastric carcinomas.

Keyword

15-hydroxyprostaglandin dehydrogenase; gastric carcinoma; methylation

MeSH Terms

Aged
Base Sequence
DNA Methylation
DNA Primers/genetics
DNA, Neoplasm/genetics
Female
Humans
Hydroxyprostaglandin Dehydrogenases/genetics/*metabolism
Male
Middle Aged
Promoter Regions, Genetic
Stomach Neoplasms/*enzymology/genetics

Figure

• 

  Fig. 1 Immunohistochemical staining and Western blot analysis of 15-PGDH in gastric carcinomas (T) and corresponding non-neoplastic tissue (N). (A) 15-PGDH was strongly expressed in both the cytoplasm of carcinoma cells and non-neoplastic mucosal epithelial cells. (B) Forty µg of protein was resolved by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. 15-PGDH, 15-hydroxyprostaglandin dehydrogenase

• 

  Fig. 2 Western blot analysis of 15-PGDH in gastric carcinomas (T) and corresponding non-neoplastic tissues (N). The expression of 15-PGDH was significantly higher in corresponding non-neoplastic tissues than in carcinomas (p < 0.05). Forty µg of protein was resolved by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents β-actin, which was used as a loading control. 15-PGDH, 15-hydroxyprostaglandin dehydrogenase.

• 

  Fig. 3 Western blot analysis of 15-PGDH and PCNA in gastric carcinomas. 15-PGDH expression was inversely correlated with PCNA expression in gastric carcinomas (p < 0.05, R = - 0.55). Forty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents β-actin, which was used as a loading control. 15-PGDH, 15-hydroxyprostaglandin dehydrogenase; PCNA, proliferating cell nuclear antigen.

• 

  Fig. 4 Correlation between 15-PGDH expression, nodal metastasis and vascular invasion in gastric carcinomas. Expression of 15-PGDH was not related to the nodal metastasis and vascular invasion in gastric carcinomas (p > 0.05). 15-PGDH, 15-hydroxyprostaglandin dehydrogenase.

• 

  Fig. 5 Western blot analysis of 15-PGDH in gastric carcinomas and methylation specific PCR with methylated 15-PGDH primer sets (M) and unmethylated 15-PGDH primer sets (U) in gastric carcinomas. The promoter methylation of 15-PGDH was not observed in 2 gastric carcinomas (T1 and T3) with negligible expression of the enzyme. 15-PGDH, 15-hydroxyprostaglandin dehydrogenase.

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