Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma
Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma
复制标题
DOI：
10.1111/j.1440-1827.2007.02204.x
复制
发表时间：
2008-03-01
影响因子：
2.2
通讯作者：
Yokozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Satake, Shinya;Semba, Shuho;Yokozaki, Hiroshi
根据胃密蛋白（claudin-18）和肠密蛋白（claudin-3和claudin-4）的表达，作者此前提出了胃癌（GC）的新表型分类：胃密蛋白（G-CLDN）、肠密蛋白（I-CLDN）和未分类的密蛋白（U-CLDN）表型。本研究的目的是研究Cdx 2，尾相关的转录因子，在体外和体内的肠道claudins表达的调节的作用。免疫组化证实，非肿瘤性胃粘膜肠上皮化生（IM）表达Cdx 2与肠claudin表达水平增加。此外，Cdx 2的表达检测28（30%）94 GC在浸润前沿。有趣的是，Cdx 2表达与I-CLDN表型显著相关（P < 0.001），这与建立的基于胃和肠粘蛋白的GC分类几乎相同。此外，将重组人CDX 2表达载体转染到TMK-1（Cdx 2阴性）GC细胞中，在mRNA（CLDN 3，3.9倍; CLDN 4，2.8倍）和蛋白质水平（claudin-3，8.6倍; claudin-4，9.8倍）上特异性提高了claudin-3和claudin-4的表达，而未检测到其他claudin的诱导。这些结果表明，Cdx 2在肠密蛋白表达的调节中起着重要作用，不仅在胃粘膜IM，但也GC。
According to the expression of gastric (claudin-18) and intestinal claudins (claudin-3 and claudin-4), the authors have previously proposed a new phenotypic classification of gastric carcinoma (GC): the gastric (G-CLDN), intestinal (I-CLDN) and unclassified claudin (U-CLDN) phenotypes. The aim of the present study was to examine the role of Cdx2, the caudal-related transcription factor, on the regulation of intestinal claudins expression in vitro and in vivo. It was confirmed on immunohistochemistry that non-neoplastic gastric mucosa with intestinal metaplasia (IM) expressed Cdx2 with increased levels of intestinal claudin expression. In addition, Cdx2 expression was detected in 28 (30%) of 94 GC at the invasive front. Interestingly, Cdx2 expression had a significant association with the I-CLDN phenotype (P < 0.001), which was almost identical to the established gastric and intestinal mucin-based GC classification. Furthermore, the transfection of a recombinant human CDX2-expressing vector into TMK-1 (Cdx2-negative) GC cells specifically elevated the expression of claudin-3 and claudin-4 at the mRNA (CLDN3, 3.9-fold; CLDN4, 2.8-fold) and protein levels (claudin-3, 8.6-fold; claudin-4, 9.8-fold), whereas no induction of the other claudins was detected. These findings suggest that Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with IM but also GC.