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Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas

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Abstract

Purpose

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), one of TGF-β superfamily gene, is reported to be responsible for NSAID-induced apoptosis. We analyzed NAG-1 expression in gastric cancer and adenoma to find out its clinical implication.

Methods

Immunostaining was performed using standard procedures with antibody to NAG-1 on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The immunoreactivity of normal and tumor tissues was graded as no, weak, moderate, and strong expression.

Results

The NAG-1 expression was stronger in intestinal metaplasia and adenoma than normal gastric epithelium. 47 (74.6%) of 63 normal gastric epithelium showed no or weak expression, but 33 (56.9%) of 58 and 13 (86.7%) of 15 intestinal metaplsia and adenoma showed moderate or strong expression. Only NAG-1 expression in diffuse type gastric cancer was weaker than in normal gastric tissue. Compared to intestinal metaplasia, both intestinal and diffuse type gastric cancer showed weaker expression. The intensity of NAG-1 expression inversely correlated with tumor differentiation and T and N stage status. While only 1 (2.2%) of 45 T1 stage cases lacked NAG-1 expression, 27 (45.8%) of 59 T3 stage cases lacked NAG-1 expression. Likewise, in N0 stage tumors only 10 (15.4%) of 65 cases lacked NAG-1 expression, but 17 (63.0%) of 27 N3 cases lacked NAG-1 expression.

Conclusions

The NAG-1 was expressed strongly in intestinal metaplasia and adenoma, and inversely correlated to tumor stages. This interesting finding may provide new targets for chemoprevention and future development of drugs.

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Acknowledgments

This study was supported in part by grant FG03-32-01 of the 21C Frontier Functional Human Genome Project from the Ministry of Science and Technology of Korea and by a grant from the Brain Korea 21 Project for Medical Sciences of Yonsei University College of Medicine.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Gastroenterology, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku, Seoul, 120-752, South Korea

    J. Y. Park, K. H. Park, S. Bang, M. H. Kim & S. Y. Song

  2. Protein Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, South Korea

    S. S. Koh

  3. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, South Korea

    S. Y. Song

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  1. J. Y. Park
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  2. K. H. Park
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  3. S. Bang
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  4. M. H. Kim
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  5. S. S. Koh
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  6. S. Y. Song
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Corresponding author

Correspondence to S. Y. Song.

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Park, J.Y., Park, K.H., Bang, S. et al. Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas. J Cancer Res Clin Oncol 134, 1029–1035 (2008). https://doi.org/10.1007/s00432-008-0362-x

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  • DOI: https://doi.org/10.1007/s00432-008-0362-x

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