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- W2991156202 abstract "866 Membrane potential and ion channels are usually studied in excitable cells. However, they appear to be involved in an increasing number of cell functions and in different pathologies. Their involvement in cell proliferation as well as in tumour invasiveness was demonstrated in several cancers. In breast cancer, the role of ion channels has been known since the work of Marino et al. in 1994 (1). Since this pioneer work, the role of ionic channels in breast cancer cell lines focused mainly on potassium channels (2, 3). The expression and the role of these channels in cell proliferation have been studied and at least 4 types of potassium channels exist in one of the most studied cell line, MCF-7 (3-5). These potassium channels are: KATP, Kv 1.1, hEAG and KCa. In the present study, we electrophysiologically investigated, by the whole-cell configuration of the patch-clamp technique, four human breast cancer cell lines: MCF-7, MDA-MB-231, MDA-MB-435s and MDA-MB-468. In all cell lines tested, we found a large-conductance, iberiotoxin-sensitive (IbTx), Ca2+-activated K+ channel (BKCa). This IbTx-sensitive conductance is increased by the Ca2+ sensitizer NS-1619. The blockade of this current by the specific blocker IbTx and its sensitization to Ca2+ by NS-1619 did not interfere with proliferation. In most tissues, this channel is well known as a key regulator of neuronal excitability, secretion, and vascular tone, by its ability to sense membrane depolarisation and increased intracellular Ca2+. Its stimulation results in an hyperpolarizing K+ current that reduces excitability. The cell lines we studied are from epithelial origin and are not excitable. Nevertheless this current has been suggested to be involved in the proliferation process of MCF-7 breast cancer cells (2, 4). From this study, we conclude that the IbTx-sensitive current, which is not involved in proliferation, is expressed in all the breast cancer cell lines studied. This suggests that this ion channel is probably expressed in normal epithelial cells and not involved in the oncogenic process. 1. A. A. Marino et al., Tumour Biol 15, 82-9 (1994). 2. J. S. Strobl, W. F. Wonderlin, D. C. Flynn, Gen Pharmacol 26, 1643-9 (Dec, 1995). 3. H. Ouadid-Ahidouch et al., Receptors Channels 7, 345-56 (2001). 4. E. A. Wegman, J. A. Young, D. I. Cook, Pflugers Arch 417, 562-70 (Feb, 1991). 5. E. Klimatcheva, W. F. Wonderlin, J Membr Biol 171, 35-46 (Sep 1, 1999)." @default.
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- W2991156202 date "2004-04-01" @default.
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- W2991156202 title "Enhancement of reactive oxygen species production by ceramide in RAW 264.7 murine macrophage activated with lipopolysaccharide and interferon-γ" @default.
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