Investigation of the molecular pathology of the differentiation mechanism by the Notch signaling pathway in colon carcinogenesis process.

本研究旨在通过大鼠结肠癌模型探讨Notch信号通路与结肠癌发生的关系。我们发现Notch 1在结肠肿瘤中的表达较正常粘膜显著增加。Klf 4在结肠癌组织中的表达明显低于正常粘膜组织。提示Notch 1的高表达和Klf 4的低表达可能与大鼠结肠癌的发生有关。我们还检查了57例受试者的结肠粘膜中使用阿辛蓝pH2.5染色的粘蛋白耗尽灶（mucin-depleted focuses，ESTA）的识别。我们发现人结肠粘膜中存在着一种蛋白质。组织学检查发现，肿瘤组织中杯状细胞丢失，细胞核肿胀，细胞核分层，淋巴细胞向间质浸润。OLL的部分代表锯齿状变化的地穴。这些结果表明，大肠癌组织中也存在大肠癌前病变，可能是大肠癌发生发展的一个有用的生物标志物。

The aim of this study is to investigate the relation of Notch signaling pathway on colon carcinogenesis by using the rats colon carcinogenic model. We found that the expression of Notch1 in colon tumor was significantly increased compared to the normal mucosa. In contrast, the expression of Klf4 in colon tumor was significantly decreased compared the normal mucosa. These results suggested that increased expression of Notch1 and decreased expression of Klf4 could be associated with the rat colon carcinogenesis. We also examined the identification of mucin-depleted foci (MDF) by using alcian blue pH2.5 stain in human colon mucosa of 57 subjects. We found that MDF existed in human colon mucosa. Histologically, MDF and OLL (Overlapped lesion with ACF) recognized the loss of goblet cells, nucleus swelling, nuclear stratification, and infiltrate of lymphocyte to stroma. The some of OLL represented the crypt with serrated change. These results suggested that MDF existed even in humans and it may be preneoplastic lesions and could be useful biomarker of human colon carcinogenesis.