Chloride ions control the G1/S cell-cycle, checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells

Chloride ions control the G1/S cell-cycle, checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells
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DOI:
10.1016/j.bbrc.2007.11.144
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发表时间:
2008-02-08
影响因子:
3.1
通讯作者:
Marunaka, Yoshinori
Marunaka, Yoshinori
中科院分区:
生物学4区
文献类型:
--
作者:
Miyazaki, Hiroaki;Shiozaki, Atsushi;Marunaka, Yoshinori

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本研究的目的是探讨氯是否影响癌细胞的细胞生长和细胞周期进展。在人胃癌MKN28细胞中,在Cl-替代培养基(NO3-替代Cl-)中培养可降低细胞内氯离子浓度([Cl-](i)),抑制细胞生长。抑制细胞生长是由于CDK2的减少和磷酸化Rb引起的细胞周期阻滞在G(0)/G(1)期。在cl -替代培养基中培养的细胞显著增加了p21 mRNA和蛋白的表达,但对p53没有影响。这些观察结果表明,氯离子在人胃癌细胞中通过p53非依赖性途径调节p21的表达,从而在细胞周期进程中发挥重要作用,从而导致通过控制[Cl-]治疗胃癌的一种新颖独特的治疗策略(i)。(c) 2007爱思唯尔公司版权所有。
The aim of the present study is to investigate whether the chloride affects cell growth and cell-cycle progression of cancer cells. In human gastric cancer MKN28 cells, the Culture in the Cl-replaced medium (replacement of Cl- by NO3-) decreased the intracellular chloride concentration ([Cl-](i)) and inhibited cell growth. The inhibition of cell growth was due to cell-cycle arrest at the G(0)/G(1) phase caused by diminution of CDK2 and phosphorylated Rb. The culture of cells in the Cl-replaced medium significantly increased expressions of p21 mRNA and protein without any effects on p53. These observations indicate that chloride ions play important roles in cell-cycle progression by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells, leading to a novel, unique therapeutic strategy for gastric cancer treatment via control of [Cl-](i). (c) 2007 Elsevier Inc. All rights reserved.