Intermediate-conductance Ca super(2+)-activated K super(+) channels (IK sub(Ca1)) regulate human prostate cancer cell proliferation through a close control of calcium entry

Accumulating data point to K super(+) 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 super(+) channels control PCa cell proliferation remain illusive. In this stud...

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Veröffentlicht in:Oncogene 2009-04, Vol.28 (15), p.1792-1806
Hauptverfasser: Lallet-Daher, H, Roudbaraki, M, Bavencoffe, A, Mariot, P, Gackiere, F, Bidaux, G, Urbain, R, Gosset, P, Delcourt, P, Fleurisse, L, Slomianny, C, Dewailly, E, Mauroy, B, Bonnal, J L, Skryma, R, Prevarskaya, N
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Sprache:eng
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Zusammenfassung:Accumulating data point to K super(+) 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 super(+) 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 (IK sub(Ca1)) in human PCa as well as their involvement in cell proliferation. We showed that IK sub(Ca1) mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK sub(Ca1) potassium channel suppressed PCa cell proliferation. The activation of IK sub(Ca1) 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 IK sub(Ca1) channel is likely to promote carcinogenesis in human prostate tissue.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2009.25