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Expression of KCNA5 Protein in Human Mammary Epithelial Cell Line Associated with Caveolin-1

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Abstract

Voltage-gated potassium (Kv) channels are involved in the proliferation and transformation of mammary epithelial cells. They are thought to be related to the development of breast carcinoma, although the exact role they play in this event remains unclear. In this study, we investigated whether the expression and function of Kv channels is associated with Caveolin-1 (Cav-1, a principal component of caveolae) in different cell lines. We found that expression of Cav-1 correlated with the expression of Kv channels in mammary epithelial cells (MCF10A, MCF10A-ST1, and MCF7), and silencing of Cav-1 inhibited the expression of KCNA5 (voltage-gated shaker-related subfamily A, member 5). Immunofluorescence analysis indicated the colocalization of KCNA5 with Cav-1, whereas immunoprecipitation suggested a possible interaction between the two proteins. Overall, our finding indicated that KCNA5 protein may interact with Cav-1, thereby contributing to the proliferation and early transformation of mammary cells.

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References

  • Abdul M, Santo A, Hoosein N (2003) Activity of potassium channel-blockers in breast cancer. Anticancer Res 23:3347–3351

    CAS  PubMed  Google Scholar 

  • Abi-Char J, Maguy A, Coulombe A, Balse E, Ratajczak P, Samuel JL, Nattel S, Hatem SN (2007) Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes. J Physiol 582:1205–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson RG, Jacobson K (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296:1821–1825

    Article  CAS  PubMed  Google Scholar 

  • Anwar SL, Wahyono A, Aryandono T, Haryono SJ (2015) Caveolin-1 in breast cancer: single molecule regulation of multiple key signaling pathways. Asian Pac J Cancer Prev 16:6803–6812

    Article  PubMed  Google Scholar 

  • Arvind S, Arivazhagan A, Santosh V, Chandramouli BA (2012) Differential expression of a novel voltage gated potassium channel—Kv 1.5 in astrocytomas and its impact on prognosis in glioblastoma. Br J Neurosurg 26(1):16–20

    Article  CAS  PubMed  Google Scholar 

  • Bielanska J, Hernández-Losa J, Moline T, Somoza R, Ramón y Cajal S, Condom E, Ferreres JC, Felipe A (2010) Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human fetus. Cell Physiol Biochem 26:219–226

    Article  CAS  PubMed  Google Scholar 

  • Bielanska J, Hernández-Losa J, Moline T, Somoza R, Ramón y Cajal S, Condom E, Ferreres JC, Felipe A (2012a) Differential expression of Kv1.3 and Kv1.5 voltage-dependent K+ channels in human skeletal muscle sarcomas. Cancer Invest 30(3):203–208

    Article  CAS  PubMed  Google Scholar 

  • Bielanska J, Hernández-Losa J, Moline T, Somoza R, Ramón y Cajal S, Condom E, Ferreres JC, Felipe A (2012b) Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness. Oncol Lett 4:227–230

    PubMed  PubMed Central  Google Scholar 

  • Chen WL, Huang XQ, Zhao LY, Li J, Chen JW, Xiao Y, Huang YY, Liu J, Wang GL, Guan YY (2012) Involvement of Kv1.5 protein in oxidative vascular endothelial cell injury. PLoS One 7:e49758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cogolludo A, Moreno L, Lodi F, Frazziano G, Cobeño L, Tamargo J, Perez-Vizcaino F (2006) Serotonin inhibits voltage-gated K+ currents in pulmonary artery smooth muscle cells: role of 5-HT2A receptors, caveolin-1, and Kv1.5 channel internalization. Circ Res 98:931–938

    Article  CAS  PubMed  Google Scholar 

  • Coiret G, Matifat F, Hague F, Ouadid-Ahidouch H (2005) 17-beta-estradiol activates maxi-K channels through a non-genomic pathway in human breast cancer cells. FEBS Lett 579:2995–3000

    Article  CAS  PubMed  Google Scholar 

  • Comes N, Bielanska J, Vallejo-Gracia A, Serrano-Albarrás A, Marruecos L, Gómez D, Soler C, Condom E, Ramón y Cajal S, Hernández-Losa J, Ferreres JC, Felipe A (2013) The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer. Front Physiol 4:283

    Article  PubMed  PubMed Central  Google Scholar 

  • Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (1997) Identification of peptide and protein liganeds for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 272:6525–6533

    Article  CAS  PubMed  Google Scholar 

  • Eldstrom J, Van Wagoner DR, Moore ED, Fedida D (2006) Localization of Kv1.5 channels in rat and canine myocyte sarcolemma. FEBS Lett 580:6039–6046

    Article  CAS  PubMed  Google Scholar 

  • Folco EJ, Liu GX, Koren G (2004) Caveolin-3 and SAP97 form a scaffolding protein complex that regulates the voltage-gated potassium channel Kv1.5. Am J Physiol Heart Circ Physiol 287:H681–H690

    Article  CAS  PubMed  Google Scholar 

  • Galbiati F, Razani B, Lisanti MP (2001) Emerging themes in lipid rafts and caveolae. Cell 106:403–411

    Article  CAS  PubMed  Google Scholar 

  • Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, Covarriubias M, Desir GV, Furuichi K, Ganetzky B, Garcia ML, Grissmer S, Jan LY, Karschin A, Kim D, Kuperschmidt S, Kurachi Y, Lazdunski M, Lesage F, Lester HA, McKinnon D, Nichols CG, O’Kelly I, Robbins J, Robertson GA, Rudy B, Sanguinetti M, Seino S, Stuehmer W, Tamkun MM, Vandenberg CA, Wei A, Wulff H, Wymore RS, International Union of Pharmacology (2003) International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacol Rev 55:583–586

    Article  CAS  PubMed  Google Scholar 

  • Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, Hayakawa T, Hamaguchi M (2001) Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res 61:2361–2364

    CAS  PubMed  Google Scholar 

  • Heubach JF, Graf EM, Leutheuser J, Bock M, Balana B, Zahanich I, Christ T, Boxberger S, Wettwer E, Ravens U (2004) Electrophysiological properties of human mesenchymal stem cells. J Physiol 554:659–672

    Article  CAS  PubMed  Google Scholar 

  • Holmes TC, Fadool DA, Ren R, Levitan IB (1996) Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science 274:2089–2091

    Article  CAS  PubMed  Google Scholar 

  • Jackson WF (2005) Potassium channels and proliferation of vascular smooth muscle cells. Circ Res 97:1211–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotecha SA, Schlichter LC (1999) A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation. J Neurosci 19:10680–10693

    CAS  PubMed  Google Scholar 

  • Liu J, Feng S, Zhang L, Wu Z, Chen Q, Cheng W, Wang SQ, Zou W (2010) Expression and properties of potassium channels in human mammary epithelial cell line MCF10A and its possible role in proliferation. Sheng Li Xue Bao 62:203–209 (Article in Chinese)

    CAS  PubMed  Google Scholar 

  • Mackenzie AB, Chirakkal H, North RA (2003) Kv1.3 potassium channels in human alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 285:L862–L868

    Article  CAS  PubMed  Google Scholar 

  • Maguy A, Hebert TE, Nattel S (2006) Involvement of lipid rafts and caveolae in cardiac ion channel function. Cardiovasc Res 69:798–807

    Article  CAS  PubMed  Google Scholar 

  • Martens JR, Navarro-Polanco R, Coppock EA, Nishiyama A, Parshley L, Grobaski TD, Tamkun MM (2000) Differential targeting of Shaker-like potassium channels to lipid rafts. J Biol Chem 275:7443–7446

    Article  CAS  PubMed  Google Scholar 

  • Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem 276:8409–8414

    Article  CAS  PubMed  Google Scholar 

  • Martens JR, O’Connell K, Tamkun M (2004) Targeting of ion channels to membrane microdomains: localization of Kv channels to lipid rafts. Trends Pharmacol Sci 25:16–21

    Article  CAS  PubMed  Google Scholar 

  • McEwen DP, Li Q, Jackson S, Jenkins PM, Martens JR (2008) Caveolin regulates Kv1.5 trafficking to cholesterol-rich membrane microdomain. Mol Pharmacol 73:678–685

    Article  CAS  PubMed  Google Scholar 

  • Michelakis ED, Weir EK (2001) The pathobiology of pulmonary hypertension: smooth muscle cells and ion channels. Clin Chest Med 22:419–432

    Article  CAS  PubMed  Google Scholar 

  • Misonou H, Trimmer JS (2004) Determinants of voltage-gated potassium channel surface expression and localization in Mammalian neurons. Crit Rev Biochem Mol Biol 39:125–145

    Article  CAS  PubMed  Google Scholar 

  • Moudgil R, Michelakis ED, Archer SL (2006) The role of K+ channels in determining pulmonary vascular tone, oxygen sensing, cell proliferation, and apoptosis: implications in hypoxic pulmonary vasoconstriction and pulmonaryarterial hypertension. Microcirculation 13(8):615–632

    Article  CAS  PubMed  Google Scholar 

  • Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A (2006) Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum Mol Genet 15:2185–2191

    Article  CAS  PubMed  Google Scholar 

  • Ouadid-Ahidouch H, Chaussade F, Roudbaraki M, Slomianny C, Dewailly E, Delcourt P, Prevarskaya N (2000) Kv1.1 K(+) channels identification in human breast carcinoma cells: involvement in cell proliferation. Biochem Biophys Res Commun 278:272–277

    Article  CAS  PubMed  Google Scholar 

  • Ouadid-Ahidouch H, Roudbaraki M, Ahidouch A, Delcourt P, Prevarskaya N (2004a) Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells. BiochemBiophys Res Commun 316:244–251

    Article  CAS  Google Scholar 

  • Ouadid-Ahidouch H, Roudbaraki M, Delcourt P, Ahidouch A, Joury N, Prevarskaya N (2004b) Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression. Am J Physiol Cell Physiol 287:C125–C134

    Article  CAS  PubMed  Google Scholar 

  • Pardo LA, del Camino D, Sánchez A, Alves F, Brüggemann A, Beckh S, Stühmer W (1999) Oncogenic potential of EAG K(+) channels. EMBO J 18:5540–5547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Potier M, Joulin V, Roger S, Besson P, Jourdan ML, Leguennec JY, Bougnoux P, Vandier C (2006) Identification of SK3 channel as a new mediator of breast cancer cell migration. Mol Cancer Ther 5:2946–2953

    Article  CAS  PubMed  Google Scholar 

  • Preussat K, Beetz C, Schrey M, Kraft R, Wölfl S, Kalff R, Patt S (2003) Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas. Neurosci Lett 346:33–36

    Article  CAS  PubMed  Google Scholar 

  • Remillard CV, Yuan JX (2004) Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol 286:L49–L67

    Article  CAS  PubMed  Google Scholar 

  • Sampson KJ, Kass RS (2010) Location, location, regulation: a novel role for beta-spectrin in the heart. J Clin Invest 120:3434–3437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shankar J, Boscher C, Nabi IR (2015) Caveolin-1, galectin-3 and lipid raft domains in cancer cell signaling. Essays Biochem 57:189–201

    Article  PubMed  Google Scholar 

  • Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110:597–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun T, Song ZG, Jiang DQ, Nie HG, Han DY (2015) Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells. J Membr Biol 248:197–204

    Article  CAS  PubMed  Google Scholar 

  • Tanabe Y, Hatada K, Naito N, Aizawa Y, Chinushi M, Nawa H, Aizawa Y (2006) Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation. Biochem Biophys Res Commun 345:1116–1121

    Article  CAS  PubMed  Google Scholar 

  • Vallejo-Gracia A, Bielanska J, Hernández-Losa J, Castellví J, Ruiz-Marcellan MC, Ramón y Cajal S, E Condom, Manils J, Soler C, Comes N, Ferreres JC, Felipe A (2013) Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy. J Leukoc Biol 94:779–789

    Article  CAS  PubMed  Google Scholar 

  • vanTol BL, Missan S, Crack J, Moser S, Baldridge WH, Linsdell P, Cowley EA (2007) Contribution of KCNQ1 to the regulatory volume decrease in the human mammary epithelial cell line MCF-7. Am J Physiol Cell Physiol 293:C1010–C1019

    Article  CAS  PubMed  Google Scholar 

  • Wang Z (2004) Roles of K+ channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch 448:274–286

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Zou W (2007) Caveolin-1 and breast cancer. Chin J Biochem Mol Biol 23:23–26 (Article in Chinese)

    CAS  Google Scholar 

  • Zou W, McDaneld L, Smith LM (2003) Caveolin-1 haploinsufficiency leads to partial transformation of human breast epithelial cells. Anticancer Res 23:4581–4586

    CAS  PubMed  Google Scholar 

  • Zou W, Zhang L, Wang X, Zhou SS (2008) Effect of potassium channel antagonist on proliferation in the human mammary epithelial cells MCF10A. J LiaoNing Norm Univ 31:213–216 (Article in Chinese)

    CAS  Google Scholar 

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Acknowledgments

We thank Dr Shisheng Zhou (Dalian Medical University, Dalian, China) for the KCNA5 protein antibody, Dr Jie Zheng (Department of Physiology and Membrane Biology, University of California, School of Medicine, Davis, USA) for pRBG4 plasimid, Dr Changsen Sun (School of Physics and Optoelectronic Engineering, Dalian University of Technology, Dalian China) and Dr Shiqiang Wang (College of Life Sciences, Peking University, Beijing, China) for the supporting of Patch-clamp experiments, Lei Zhang (College of Life Science, Liaoning Normal University, Dalian China) and Qian Chen (College of Life Science, Liaoning Normal University, Dalian China) for the supporting of Western blot experiments. We also thank Dr Alan K Chang (Liaoning University, Shenyang, China) for helpful discussion and for revising the language of the manuscript. This project was supported by the National Natural Science Foundation of China (No. 30570225 and 30970353), and Science and Technology Plan Projects in Liaoning Province, China (No. 201501522).

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    Authors and Affiliations

    1. Department of Biological Science and Technology, Dalian University of Technology, Dalian, 116024, China

      Jia Liu & Lijia An

    2. College of Life Science, Liaoning Normal University, No. 1, The South Street of Liushu, Dalian, 116029, China

      Jia Liu, Chao Qu, Hongyan Li, Yejun Zhang, Jia Sun, Shuo Yang & Wei Zou

    3. Centre of Regenerative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

      Jing Liu

    4. Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, Dalian, 116029, China

      Hongyan Li, Yejun Zhang & Wei Zou

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    1. Jia Liu
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    Correspondence to Wei Zou.

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    Jia Liu, Chao Qu and Hongyan Li contributed equally to this work.

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    Liu, J., Qu, C., Li, H. et al. Expression of KCNA5 Protein in Human Mammary Epithelial Cell Line Associated with Caveolin-1. J Membrane Biol 249, 449–457 (2016). https://doi.org/10.1007/s00232-016-9885-2

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