A regulatory role of K⁺-Cl^? cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells

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• 作者：Maki Kitagawa ; Naomi Niisato ; Atsushi Shiozaki ; Mariko Ohta-Fujimoto ; Shigekuni Hosogi ; Hiroaki Miyazaki ; Daisuke Ichikawa ; Eigo Otsuji ; Yoshinori Marunaka
• 关键词：K+&ndash ; Cl&minus ; cotransporter ; Cell cycle ; Cyclin D1 ; Cyclin E2 ; p21
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2013
• 出版时间：1 November, 2013
• 年：2013
• 卷：539
• 期：1
• 页码：92-98
• 全文大小：980 K

文摘

K⁺-Cl^? cotransporter (KCC) has been shown to be involved in cell proliferation as well as cell volume regulation. A regulatory role of KCC in cell cycle progression of breast cancer MDA-MB-231 cells was explored by using synchronized MDA-MB-231 cells and dihydro-indenyloxy-alkanoic acid (DIOA), a potent inhibitor of KCC. MDA-MB-231 cells cultured in the presence of DIOA exhibited an increase in cell volume, a decrease in intracellular Cl^? concentration, and reduction in cell proliferation with the G₀/G₁ phase arrest, which was accompanied with down-regulation of cyclin D1 and cyclin E2, and up-regulation of p21. Among these molecules, the expression of cyclin E2, a molecule essential for the transition from G₁ to S phase, was markedly suppressed by DIOA treatment. DIOA-mediated up- or down-regulation of these molecules occurred at the transcriptional level. These findings suggest that KCC plays an important role in the early phase of cell cycle progression by regulating the expression of cyclin D1, cyclin E2, and p21, the molecules essential for the cell cycle progression.