Aberrant expression of SOX9 is associated with gastrokine 1 inactivation in gastric cancers

Abstract

Background: SOX9 belongs to the SOX [sry-related high-mobility group (HMG) box] family and acts as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages. The aim of this study was to determine whether the GKN1 gene is involved in the development of gastric cancer by regulating SOX9. Methods: The effect of GKN1 and β-catenin on SOX9 expression was examined in GKN1 and β-catenin- transfected AGS and MKN-1 gastric cancer cells. SOX9 expression was also determined in gastric cancer tissues and cell lines by Western blot analysis and immunohistochemistry. Results: Ectopic expression of β-catenin induced increased expression of SOX9 in AGS cells, whereas GKN1 decreased expression of SOX9 in AGS and MKN-1 cells. In addition, we found an inverse correlation between expression of SOX9 and GKN1 in gastric cancer tissues and cell lines. In immunohistochemistry, nuclear SOX9 expression was detected in 64 (34.6 %) of 185 gastric carcinomas and its expression was closely associated with GKN1 immunonegativity. There was no significant relationship between altered expression of SOX9 protein and clinicopathological parameters including overall survival. Conclusion: These data suggest that aberrant SOX9 expression by GKN1 inactivation may be involved in the development of sporadic gastric cancers as an early event. © 2013 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.