Li Qing Lin, Ito Kosei, Sakakura Chohei, Fukamachi Hiroshi, Inoue Ken ichi, Chi Xin Zi, Lee Kwang Youl, Nomura Shintaro, Lee Chang Woo, Han Sang Bae, Kim Hwan Mook, Kim Wun Jae, Yamamoto Hiromitsu, Yamashita Namiko, Yano Takashi, Ikeda Toshio, Itohara Shigeyoshi, Inazawa Johji, Abe Tatsuo, Hagiwara Akeo, Yamagishi Hisakazu, Ooe Asako, Kaneda Atsushi, Sugimura Takashi, Ushijima Toshikazu, Bae Suk Chul, Ito Yoshiaki
Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, 361-763, Cheongju, South Korea.
Cell. 2002 Apr 5;109(1):113-24. doi: 10.1016/s0092-8674(02)00690-6.
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.
Runx3/Pebp2alphaC基因敲除小鼠的胃黏膜由于上皮细胞增殖受刺激和凋亡受抑制而出现增生，并且这些细胞对转化生长因子-β（TGF-β）的生长抑制和凋亡诱导作用具有抗性，这表明Runx3是胃上皮细胞的主要生长调节因子。由于RUNX3启动子区域的半合子缺失和高甲基化，45%至60%的人类胃癌细胞不显著表达RUNX3。人类胃癌细胞系在裸鼠中的致瘤性与其RUNX3表达水平呈负相关，并且在保守的Runt结构域内发生的一个突变（R122C）消除了RUNX3的肿瘤抑制作用，这表明RUNX3功能的缺失与人类胃癌的发生和发展存在因果关系。
