SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis.
SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis.
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DOI：
10.1038/sj.bjc.6604193
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发表时间：
2008-02-26
影响因子：
8.8
通讯作者：
Yuasa, Y.
中科院分区：
文献类型：
--
作者：
Otsubo, T.;Akiyama, Y.;Yanagihara, K.;Yuasa, Y.
SOX转录因子是胚胎发育所必需的，并在细胞命运决定、分化和增殖中发挥关键作用。我们以前报道过SOX 2蛋白在正常胃粘膜中表达，但在某些人胃癌中下调。为了阐明SOX 2在胃癌发生中的作用，我们在胃上皮细胞系中进行了SOX 2的功能表征。外源性表达SOX 2抑制胃上皮细胞系的细胞增殖。流式细胞仪分析显示，SOX 2过表达的细胞表现出细胞周期阻滞和凋亡。我们发现，SOX 2介导的细胞周期阻滞与细胞周期蛋白D1和磷酸化Rb的水平降低，以及p27 Kip 1水平升高有关。这些细胞表现出凋亡的进一步特征，如DNA梯状和caspase-3激活。在一些培养的和原发性胃癌中观察到SOX 2高甲基化信号，而没有或弱表达SOX 2。在52例晚期胃癌患者中，那些显示SOX 2甲基化的癌症患者的生存时间明显短于那些没有这种甲基化的患者（P=0.0062）。因此，SOX 2在胃上皮细胞中通过细胞周期阻滞和细胞凋亡发挥重要的生长抑制作用，SOX 2表达的缺失可能与胃癌的发生和预后不良有关。
SOX transcription factors are essential for embryonic development and play critical roles in cell fate determination, differentiation and proliferation. We previously reported that the SOX2 protein is expressed in normal gastric mucosae but downregulated in some human gastric carcinomas. To clarify the roles of SOX2 in gastric carcinogenesis, we carried out functional characterisation of SOX2 in gastric epithelial cell lines. Exogenous expression of SOX2 suppressed cell proliferation in gastric epithelial cell lines. Flow cytometry analysis revealed that SOX2-overexpressing cells exhibited cell-cycle arrest and apoptosis. We found that SOX2-mediated cell-cycle arrest was associated with decreased levels of cyclin D1 and phosphorylated Rb, and an increased p27Kip1 level. These cells exhibited further characteristics of apoptosis, such as DNA laddering and caspase-3 activation. SOX2 hypermethylation signals were observed in some cultured and primary gastric cancers with no or weak SOX2 expression. Among the 52 patients with advanced gastric cancers, those with cancers showing SOX2 methylation had a significantly shorter survival time than those without this methylation (P=0.0062). Hence, SOX2 plays important roles in growth inhibition through cell-cycle arrest and apoptosis in gastric epithelial cells, and the loss of SOX2 expression may be related to gastric carcinogenesis and poor prognosis.
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DOI：
10.1083/jcb.200409182
发表时间：
2005-03-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mansukhani A;Ambrosetti D;Holmes G;Cornivelli L;Basilico C
通讯作者：
Basilico C
DOI：
10.1007/s00432-006-0165-x
发表时间：
2007-04-01
影响因子：
3.6
作者：
Tani, Yasuyo;Akiyama, Yoshimitsu;Yuasa, Yasuhito
通讯作者：
Yuasa, Yasuhito
按地点划分的全球和区域癌症死亡率和发病率估计：II。 2000 年全球疾病负担的结果。
影响因子：
3.8
作者：
Shibuya, K;Mathers, CD;Boschi-Pinto, C;Lopez, AD;Murray, CJL
通讯作者：
Murray, CJL
影响因子：
11.2
作者：
Aaboe, M;Birkenkamp-Demtroder, K;Orntoft, T
通讯作者：
Orntoft, T
影响因子：
24.5
作者：
Eguchi, H;Carpentier, S;Moss, SF
通讯作者：
Moss, SF