Department of Medicine, Division of Gastroenterology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Differentiation. 2011 Feb;81(2):92-8. doi: 10.1016/j.diff.2010.10.002. Epub 2010 Oct 30.
Sox2 is closely related to the gastric phenotype. Sox2 plays a pivotal role in gastric epithelial differentiation in the adult. Sox2 expression is reduced in Helicobacter pylori-associated intestinal metaplastic change of the gastric epithelium. The gastric mucosa is replaced by intestinal metaplastic mucosa in the stomach of caudal type homeobox 2 (Cdx2)-transgenic mice. The aim of this study was to use Cdx2-transgenic mice to investigate: (i) Sox2 expression in the intestinal metaplastic mucosa of the Cdx2-transgenic mouse stomach; and (ii) the relationship between Sox2 and Cdx2. Quantitative real-time PCR was performed to determine Sox2, Cdx2, Muc5Ac, and alkaline phosphatase mRNA expression levels and single- or double-label immunohistochemistry was used to evaluate the localization of Sox2, Cdx2, gastric mucin and alkaline phosphatase activity. We determined that Sox2 mRNA in the intestinal metaplastic mucosa of the Cdx2-transgenic mouse stomach was expressed 3.5-fold compared to the normal mouse stomach. Immunohistochemical analysis showed that the same cells in the intestinal metaplastic mucosa expressed both Cdx2 and Sox2. Gastric mucin was not expressed while alkaline phosphatase activity was recognized in the intestinal metaplastic mucosa in spite of the Sox2 expression. Cdx2 increased the transcriptional activity of the Sox2 gene, and Sox2 increased the transcriptional activity of the Muc5Ac gene, which was reduced by cotransfecion of Cdx2 together with Sox2 in the human gastric carcinoma cell line AGS. In conclusion, Sox2 expression is maintained while gastric phenotype is completely lost in the intestinal metaplastic mucosa of Cdx2-transgenic mouse stomach.
Sox2 与胃表型密切相关。Sox2 在成人胃上皮分化中起关键作用。Sox2 在幽门螺杆菌相关的胃上皮肠化生中的表达减少。尾型同源盒 2（Cdx2）转基因小鼠的胃黏膜被肠化生黏膜取代。本研究旨在使用 Cdx2 转基因小鼠来研究：（i）Cdx2 转基因小鼠胃肠化生黏膜中的 Sox2 表达；（ii）Sox2 与 Cdx2 之间的关系。采用定量实时 PCR 测定 Sox2、Cdx2、Muc5Ac 和碱性磷酸酶 mRNA 表达水平，并用单标或双标免疫组化评估 Sox2、Cdx2、胃粘蛋白和碱性磷酸酶活性的定位。我们发现 Cdx2 转基因小鼠胃肠化生黏膜中的 Sox2 mRNA 表达水平是正常小鼠胃的 3.5 倍。免疫组化分析显示，肠化生黏膜中的相同细胞同时表达 Cdx2 和 Sox2。尽管 Sox2 表达，但胃粘蛋白未表达，而碱性磷酸酶活性在肠化生黏膜中被识别。Cdx2 增加了 Sox2 基因的转录活性，而 Sox2 增加了 Muc5Ac 基因的转录活性，Cdx2 与 Sox2 共转染可降低 AGS 人胃癌细胞系中的 Muc5Ac 基因转录活性。总之，在 Cdx2 转基因小鼠胃的肠化生黏膜中，胃表型完全丧失，但 Sox2 表达仍被维持。
