title: 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.
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 NO(3)(-)) 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).
authors: Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors: Hiroaki
authors: H
authors: Miyazaki
authors: Atsushi
authors: A
authors: Shiozaki
authors: Naomi
authors: N
authors: Niisato
authors: Rumi
authors: R
authors: Ohsawa
authors: Hirosumi
authors: H
authors: Itoi
authors: Yuji
authors: Y
authors: Ueda
authors: Eigo
authors: E
authors: Otsuji
authors: Hisakazu
authors: H
authors: Yamagishi
authors: Yoshinobu
authors: Y
authors: Iwasaki
authors: Takashi
authors: T
authors: Nakano
authors: Takashi
authors: T
authors: Nakahari
authors: Yoshinori
authors: Y
authors: Marunaka
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002713:Chlorine / Q000008:administration & dosage*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007477:Ions; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007477:Ions; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002713:Chlorine