K+ Channel Expression in Human Breast Cancer Cells: Involvement in Cell Cycle Regulation and Carcinogenesis

K+ channels are a most diverse class of ion channels in the plasma membrane and are distributed widely throughout a variety of cells including cancer cells. Evidence has been accumulating from fundamental studies indicating that tumour cells possess various types of K+ channels and that these K+ channels play important roles in regulating tumor cell proliferation, cell cycle progression and apoptosis. Moreover, a significant increase in K+ channel expression has been correlated with tumorigenesis, suggesting the possibility of using these proteins as transformation markers and perhaps reducing the tumor growth rate by selectively inhibiting their functional activity. Significant progress has been made in defining the properties of breast K+ channels, including their biophysical and pharmacological properties and distribution throughout different phases of the cell cycle in breast cell line MCF-7. This review aims to provide a comprehensive overview of the current state of research into K+ channels/currents in breast cancer cells. The possible mechanisms by which K+ channels affect tumor cell proliferation and cell cycle progression are discussed.

[1]  W. Wonderlin,et al.  Inhibition of ATP‐sensitive potassium channels causes reversible cell‐cycle arrest of human breast cancer cells in tissue culture , 1995, Journal of cellular physiology.

[2]  L. Pardo,et al.  Oncogenic potential of EAG K+ channels , 1999, The EMBO journal.

[3]  L. Lu,et al.  Modulation of Rabbit Corneal Epithelial Cell Proliferation by Growth Factor-regulated K+ Channel Activity , 2003, The Journal of Membrane Biology.

[4]  W. Wonderlin,et al.  Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF‐7 human breast carcinoma cell line , 1998, Journal of cellular physiology.

[5]  A. G. Cooper,et al.  Overexpression of the G-protein inwardly rectifying potassium channel 1 (GIRK1) in primary breast carcinomas correlates with axillary lymph node metastasis. , 2001, Cancer research.

[6]  W. Wonderlin,et al.  An ATP-Sensitive K+ Current that Regulates Progression Through Early G1 Phase of the Cell Cycle in MCF-7 Human Breast Cancer Cells , 1999, The Journal of Membrane Biology.

[7]  P. Cohen,et al.  IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1 , 2002, Pflügers Archiv - European Journal of Physiology.

[8]  M. Roudbaraki,et al.  Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression. , 2004, American journal of physiology. Cell physiology.

[9]  W. Dai,et al.  Insulin-activated, K+-channel-sensitive Akt pathway is primary mediator of ML-1 cell proliferation. , 2005, American journal of physiology. Cell physiology.

[10]  L. Pardo,et al.  Overexpression of Eag1 potassium channels in clinical tumours , 2006, Molecular Cancer.

[11]  G. L. Carter,et al.  Calcium ion-dependent proliferation of L1210 cells in culture. , 1987, Biochemical and biophysical research communications.

[12]  G. Hunninghake,et al.  Interleukin‐4 inhibits lipopolysaccharide‐induced expression of prostaglandin H synthase‐2 in human alveolar macrophages , 1995, Journal of cellular physiology.

[13]  A. Manni,et al.  TGF-α and IGF-I effects on calcium ion transients in human breast cancer cells , 1992 .

[14]  S. Moreno,et al.  Regulation of G1 progression in fission yeast by the rum1+ gene product. , 1996, Progress in cell cycle research.

[15]  M. Pellegrino,et al.  Modulation of Ca2+-activated K+ channels of human erythrocytes by endogenous cAMP-dependent protein kinase , 1998, Pflügers Archiv.

[16]  C. Slomianny,et al.  KV1.1 K(+) channels identification in human breast carcinoma cells: involvement in cell proliferation. , 2000, Biochemical and biophysical research communications.

[17]  P. Bodine,et al.  Related effects of calcium and serum on the G1 phase of the human WI38 fibroblast , 1980, Journal of cellular physiology.

[18]  M. Pellegrino,et al.  Modulation of Ca 2 +-activated K + channels of human erythrocytes by endogenous cAMP-dependent protein kinase , 2022 .

[19]  B. Nilius,et al.  Potassium channels and regulation of proliferation of human melanoma cells. , 1992, The Journal of physiology.

[20]  L. Pardo,et al.  Role of Voltage-gated Potassium Channels in Cancer , 2005, The Journal of Membrane Biology.

[21]  Mansoor Abdul,et al.  Activity of potassium channel-blockers in breast cancer. , 2003, Anticancer research.

[22]  W. Wonderlin,et al.  Changes in membrane potential during the progression of MCF‐7 human mammary tumor cells through the cell cycle , 1995, Journal of cellular physiology.

[23]  Andrew A. Marino,et al.  Association between cell membrane potential and breast cancer. , 1994, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[24]  F. Gouilleux,et al.  IGF‐1 activates hEAG K+ channels through an Akt‐dependent signaling pathway in breast cancer cells: Role in cell proliferation , 2007, Journal of cellular physiology.

[25]  F. Lang,et al.  Ion Channels in Cell Proliferation and Apoptotic Cell Death , 2005, The Journal of Membrane Biology.

[26]  D. Devor,et al.  Kinase-dependent Regulation of the Intermediate Conductance, Calcium-dependent Potassium Channel, hIK1* , 2000, The Journal of Biological Chemistry.

[27]  Zhiguo Wang.  Roles of K+ channels in regulating tumour cell proliferation and apoptosis , 2004, Pflügers Archiv.

[28]  B. Mitchell,et al.  Calcium, magnesium, and growth control in the WI-38 human fibroblast cell , 1979, The Journal of cell biology.

[29]  R. Toillon,et al.  Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. , 2001, Receptors & channels.

[30]  A. Czarnecki,et al.  Potassium channel expression level is dependent on the proliferation state in the GH3 pituitary cell line. , 2003, American journal of physiology. Cell physiology.

[31]  W. Wonderlin,et al.  Mitogenic signal transduction in human breast cancer cells. , 1995, General pharmacology.

[32]  Vera V. Koledova,et al.  Ca2+, calmodulin, and cyclins in vascular smooth muscle cell cycle. , 2006, Circulation research.

[33]  K. Kunzelmann.  Ion Channels and Cancer , 2005, The Journal of Membrane Biology.

[34]  J. McCubrey,et al.  Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase kinase participate in the control of cell cycle progression in MCF-7 human breast cancer cells. , 2005, Cancer research.

[35]  T. Heckman,et al.  Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  L. Pardo,et al.  Potassium channels as tumour markers , 2006, FEBS letters.

[37]  W. Dai,et al.  A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells. , 1999, Blood.

[38]  L. Kaczmarek,et al.  hSK4/hIK1, a Calmodulin-binding KCa Channel in Human T Lymphocytes , 1999, The Journal of Biological Chemistry.

[39]  J. Le Guennec,et al.  Description and role in proliferation of iberiotoxin-sensitive currents in different human mammary epithelial normal and cancerous cells. , 2004, Biochimica et biophysica acta.

[40]  M. Roudbaraki,et al.  Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells. , 2004, Biochemical and biophysical research communications.

[41]  D. Escande,et al.  ATP-sensitive K+ channels regulated by intracellular Ca2+ and phosphorylation in normal (T84) and cystic fibrosis (CFPAC-1) epithelial cells , 2004, Pflügers Archiv.

[42]  A. Means,et al.  Regulation of the cell cycle by calcium and calmodulin. , 1993, Endocrine reviews.

[43]  W. Wonderlin,et al.  Potassium Channels, Proliferation and G1 Progression , 1996, The Journal of Membrane Biology.

[44]  D. Cook,et al.  A 23-pS Ca2+-activated K+ channel in MCF-7 human breast carcinoma cells: an apparent correlation of channel incidence with the rate of cell proliferation , 1991, Pflügers Archiv.

[45]  O. Bachs,et al.  Calcium and Calmodulin Function in the Cell Nucleus , 1995, Molecular Biology Intelligence Unit.

[46]  S. Heinemann,et al.  Inhibition of human ether à go‐go potassium channels by Ca2+/calmodulin , 2000, The EMBO journal.

[47]  A. Janowsky,et al.  Domains Responsible for Constitutive and Ca2+-Dependent Interactions between Calmodulin and Small Conductance Ca2+-Activated Potassium Channels , 1999, The Journal of Neuroscience.

[48]  L. Pardo.  Voltage-gated potassium channels in cell proliferation. , 2004, Physiology.

[49]  L. Santella,et al.  Review The cell cycle: a new entry in the field of Ca 2+ signaling , 2005 .

[50]  M. Wigler,et al.  Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. , 2003, Cancer cell.

[51]  K. Chandy,et al.  Calmodulin Mediates Calcium-dependent Activation of the Intermediate Conductance KCa Channel,IKCa1 * , 1999, The Journal of Biological Chemistry.

[52]  S. Heinemann,et al.  Identification of Ether à Go-Go and Calcium-Activated Potassium Channels in Human Melanoma Cells , 1999, The Journal of Membrane Biology.