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Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Oncogene volume 28, pages 1792–1806 (2009)Cite this article

Abstract

Accumulating data point to K+ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K+ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IKCa1) in human PCa as well as their involvement in cell proliferation. We showed that IKCa1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IKCa1 potassium channel suppressed PCa cell proliferation. The activation of IKCa1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IKCa1 channel is likely to promote carcinogenesis in human prostate tissue.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

1-EBIO:

1-ethyl-2-benzimidazolinone

BK:

Ca2+-activated K+ channel with big conductance

CCE:

capacitative calcium entry

IKCa1:

Ca2+-activated K+ channel with intermediate conductance

RT–PCR:

reverse transcription–PCR

TRAM-34:

1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole

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Acknowledgements

We thank Dr Y Shuba (Bogomoletz Institute of Physiology, Kiev, Ukraine) for helpful discussions. This study was supported by grants from INSERM, the Ministère de l'Education Nationale de l'Enseignement Supérieur et de la Recherche, La Ligue Nationale Contre le Cancer. H Lallet-Daher was supported by the Association pour la Recherche sur les Tumeurs de la Prostate (ARTP). We also thank Dr Mao Xiang Chen (Laboratory of Gene Expression and Protein Biochemistry, GlaxoSmithKline R&D, UK) for the generous gift of the IKCa1 antibodies.

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Author notes

  1. H Lallet-Daher and M Roudbaraki: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM U800, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France

    H Lallet-Daher, M Roudbaraki, A Bavencoffe, P Mariot, F Gackière, G Bidaux, P Delcourt, C Slomianny, E Dewailly, R Skryma & N Prevarskaya

  2. Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France

    H Lallet-Daher, M Roudbaraki, A Bavencoffe, P Mariot, F Gackière, G Bidaux, P Delcourt, C Slomianny, E Dewailly, R Skryma & N Prevarskaya

  3. Institut de Recherche Pierre Fabre, Paris, France

    R Urbain

  4. Faculté Libre de Médecine, Laboratoire d'Anatomie et de Cytologie Pathologique du groupement hospitalier de l'Institut Catholique de Lille, Lille, France

    P Gosset & L Fleurisse

  5. Service d'Urologie de l'hôpital St-Philibert, Lomme, France

    B Mauroy & J L Bonnal

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  1. H Lallet-Daher
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  2. M Roudbaraki
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  14. J L Bonnal
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  15. R Skryma
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  16. N Prevarskaya
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Corresponding authors

Correspondence to M Roudbaraki or N Prevarskaya.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Lallet-Daher, H., Roudbaraki, M., Bavencoffe, A. et al. Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry. Oncogene 28, 1792–1806 (2009). https://doi.org/10.1038/onc.2009.25

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