Causal relationship between the loss of RUNX3 expression and gastric cancer
Causal relationship between the loss of RUNX3 expression and gastric cancer
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DOI：
10.1016/s0092-8674(02)00690-6
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发表时间：
2002-04-05
期刊：
影响因子：
64.5
通讯作者：
Ito, Y
中科院分区：
文献类型：
--
作者：
Li, QL;Ito, K;Ito, Y
Runx3/Pebp2alphaC缺失小鼠胃粘膜由于刺激上皮细胞增殖和抑制凋亡而出现增生，且细胞对tgf - β的生长抑制和诱导凋亡作用具有抗性，表明Runx3是胃上皮细胞的主要生长调节剂。45% - 60%的人胃癌细胞由于RUNX3启动子区域的半合子缺失和高甲基化而不显著表达RUNX3。裸鼠人胃癌细胞系的致瘤性与其RUNX3表达水平呈负相关，在Runt保守结构域发生的突变（R122C）使RUNX3的抑瘤作用消失，提示RUNX3功能缺失与人胃癌的发生发展有因果关系。
Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.