Abstract 2205: Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas

Abstract Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The aim of this study is to determine whether inactivation of the GKN1 gene is involved in the development and/or progression of the gastric cancers. GKN1 expression was examined in gastric adenomas and cancer by immunohistochemistry and Western blot analysis. We also analyzed mutation and epigenetic alteration, DNA copy number change and mRNA transcript of GKN1 in gastric adenomas and carcinomas. The effect of GKN1 on cell proliferation and death was further examined in wild-type GKN1 transfected AGS gastric cancer cells. In immunohistochemistry, reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathologic parameters, including depth of invasion, location, and lymph node metastasis (Chi-Square test, P>0.05). In Western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumors, and hypermethylation of GKN1 gene was found in 2 gastric cancers. Interestingly, DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2011-2205