Growth regulation of gastric epithelial cells by Runx3
Growth regulation of gastric epithelial cells by Runx3
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DOI：
10.1038/sj.onc.1207121
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发表时间：
2004-05-24
期刊：
影响因子：
8
通讯作者：
Ito, K
中科院分区：
文献类型：
--
作者：
Fukamachi, H;Ito, K
Runx3 在整个发育过程中由胃上皮细胞表达。 Runx3基因被敲除的小鼠在出生后不久就死亡。在基因敲除小鼠中，胃上皮表现出增生，上皮细胞凋亡受到抑制。使用原代培养系统对上皮细胞进行的分析表明，这是由于 Runx3 -/- 胃上皮细胞对 TGF-β 的生长抑制和凋亡诱导活性的敏感性降低所致。在人和小鼠胃癌细胞系中，RUNX3/Runx3 由于启动子区域 CpG 岛的高甲基化而被沉默。在不表达内源基因的细胞中外源表达RUNX3会导致体内和体外生长的抑制。这些观察结果表明Runx3是胃上皮细胞的主要生长调节剂，并且它深深参与人类和小鼠的胃肿瘤发生。
Runx3 is expressed by gastric epithelial cells throughout development. Mice whose Runx3 gene has been knocked out died soon after birth. In the knockout mouse, gastric epithelia exhibited hyperplasia and epithelial apoptosis was suppressed. Analysis using a primary culture system for the epithelial cells suggested that this is caused by the reduced sensitivity of Runx3 -/- gastric epithelial cells to the growth-inhibiting and apoptosis-inducing activities of TGF-beta. In human and mouse gastric cancer cell lines, RUNX3/Runx3 was silenced due to hypermethylation of CpG islands in the promoter region. Exogenous expression of RUNX3 in the cells that do not express the endogenous gene caused an inhibition of growth both in vivo and in vitro. These observations indicate that Runx3 is a major growth regulator of gastric epithelial cells, and that it is deeply involved in gastric tumorigenesis in both humans and mice.