title: A regulatory role of K(+)-Cl(-) cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells.
abstract: 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.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan; Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: icam-s@koto.kpu-m.ac.jp.
authors.forename: Maki
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Niisato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Mariko
authors.initials: M
authors.lastname: Ohta-Fujimoto
authors.forename: Shigekuni
authors.initials: S
authors.lastname: Hosogi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D027981:Symporters; D000096922:K Cl- Cotransporters; C503688:CCNE2 protein, human; C493956:CDKN1A protein, human
keywords: Cell cycle; Cyclin D1; Cyclin E2; K(+)–Cl(−) cotransporter; p21