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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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| Authors: | Miyazaki Hiroaki Shiozaki Atsushi Niisato Naomi Ohsawa Rumi Itoi Hirosumi Ueda Yuji Otsuji Eigo Yamagishi Hisakazu Iwasaki Yoshinobu Nakano Takashi Nakahari Takashi Marunaka Yoshinori |
| Institution: | a Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan b Department of Surgery, Division of Digestive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan c Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan d Department of Surgery, Graduate School of Acupuncture and Moxibustion, Meiji University of Oriental Medicine, Nantan 629-0392, Japan e Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki 569-8686, Japan f Department of Physiology, Osaka Medical College, Takatsuki 569-8686, Japan |
| Abstract: | 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 G0/G1 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. |
| Keywords: | Intracellular chloride Cell proliferation Cell cycle p21 Gastric cancer |
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