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首页> 外文期刊>Journal of Cellular Physiology >Epithelial cell adhesion molecule fragments and signaling in primary human liver cells
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Epithelial cell adhesion molecule fragments and signaling in primary human liver cells

机译：上皮细胞粘附分子和碎片人类肝细胞信号在初级

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摘要

Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans‐membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cleavage of the extracellular domain. Within the cell nucleus, it induces cell proliferation, but cleavage depends on cell contact. Fragments of various lengths have been described in tumor cells. Despite its described important role in proliferation in tumor cells, there is not much known about the expression and role of EpCAM fragments in primary human liver cells. Here, we demonstrate that EpCAM protein fragments and function are considerable different between tumor cells, normal fetal and adult liver cells. Contrary to previously reported findings in tumor cells, gene knockdown or treatment with an inhibitor of the cleavage enzyme ADAM17 (TACE) rather increased cell numbers in primary human fetal liver‐derived EpCAM‐positive cells. EpCAM fragment sizes were not affected by treatment with inhibitor. Knockdown of EPCAM gene expression by siRNA in sorted cells did not significantly affect proliferation‐associated genes or cell numbers. The intracellular domain could not be detected within cell nuclei of fetal and adult liver cells. In conclusion, signaling through the intracellular domain of EpCAM appears to be a mechanism that induces proliferation specifically in tumorigenic cells but not in normal primary EpCAM‐positive liver cells.
机译：上皮细胞粘附分子(EpCAM),或CD326,是一个跨膜糖蛋白表达由多个正常上皮细胞以及癌。肝脏上皮EpCAM是积极的。肿瘤细胞系,其胞内域发布后细胞外的乳沟域。增殖,但乳沟取决于细胞接触。在肿瘤细胞中描述。重要的作用在肿瘤细胞增殖,并没有多少了解的表达式EpCAM碎片在初级人类肝脏的作用细胞。碎片和功能是相当不同的肿瘤细胞间正常胎儿和成人肝脏细胞。在肿瘤细胞中,基因击倒或治疗裂解酶的抑制剂ADAM17 (TACE)而在主要人类细胞数量增加胎儿肝脏派生EpCAM检测阳性的细胞。片段大小不影响治疗抑制剂。核表达的细胞没有分类明显影响扩散有关基因或细胞数量。不能检测到细胞核内胎儿吗和成人肝细胞。通过胞内域EpCAM出现是一个机制,诱导增殖特别是在致瘤的细胞而不是正常的主要EpCAM积极的肝细胞。

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