Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
Gastric Cancer. 2014 Apr;17(2):247-54. doi: 10.1007/s10120-013-0277-3. Epub 2013 Jun 28.
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.
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.
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.
These data suggest that aberrant SOX9 expression by GKN1 inactivation may be involved in the development of sporadic gastric cancers as an early event.
SOX9 属于 SOX（性别决定区 Y 框）家族，作为转录因子，在多种细胞谱系的发育和分化中发挥核心作用。本研究旨在通过调节 SOX9 来确定 GKN1 基因是否参与胃癌的发生。
通过转染 GKN1 和 β-catenin ，检测 GKN1 和 β-catenin 对 AGS 和 MKN-1 胃癌细胞中 SOX9 表达的影响。通过 Western blot 分析和免疫组织化学检测胃癌组织和细胞系中 SOX9 的表达。
β-catenin 的异位表达诱导 AGS 细胞中 SOX9 的表达增加，而 GKN1 则降低 AGS 和 MKN-1 细胞中 SOX9 的表达。此外，我们发现胃癌组织和细胞系中 SOX9 和 GKN1 的表达呈负相关。免疫组织化学检测到 185 例胃癌中的 64 例（34.6%）存在核 SOX9 表达，其表达与 GKN1 免疫阴性密切相关。SOX9 蛋白表达改变与包括总生存期在内的临床病理参数之间无显著相关性。
这些数据表明，GKN1 失活导致 SOX9 表达异常可能参与散发性胃癌的发生，这是一个早期事件。
