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

H Lallet-Daher; M Roudbaraki; A Bavencoffe; P Mariot; F Gackière; G Bidaux; R Urbain; P Gosset; P Delcourt; L Fleurisse; C Slomianny; E Dewailly; B Mauroy; J L Bonnal; R Skryma; N Prevarskaya

doi:10.1038/onc.2009.25

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

Oncogene. 2009 Apr 16;28(15):1792-806. doi: 10.1038/onc.2009.25. Epub 2009 Mar 9.

Authors

H Lallet-Daher¹, M Roudbaraki, A Bavencoffe, P Mariot, F Gackière, G Bidaux, R Urbain, P Gosset, P Delcourt, L Fleurisse, C Slomianny, E Dewailly, B Mauroy, J L Bonnal, R Skryma, N Prevarskaya

Affiliation

¹ INSERM U800, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.

PMID: 19270724
DOI: 10.1038/onc.2009.25

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 (IK(Ca1)) in human PCa as well as their involvement in cell proliferation. We showed that IK(Ca1) mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK(Ca1) potassium channel suppressed PCa cell proliferation. The activation of IK(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(Ca1) channel is likely to promote carcinogenesis in human prostate tissue.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzimidazoles / pharmacology
Calcium / metabolism*
Calcium Channels / physiology
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 / analysis
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p27
G1 Phase
Humans
Intermediate-Conductance Calcium-Activated Potassium Channels / analysis
Intermediate-Conductance Calcium-Activated Potassium Channels / physiology*
Intracellular Signaling Peptides and Proteins / analysis
Male
Membrane Potentials
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology*
RNA, Messenger / analysis
S100 Proteins / analysis
TRPV Cation Channels / physiology
Tumor Suppressor Protein p53 / physiology

Substances

Benzimidazoles
CDKN1A protein, human
CDKN1B protein, human
Calcium Channels
Cyclin-Dependent Kinase Inhibitor p21
Intermediate-Conductance Calcium-Activated Potassium Channels
Intracellular Signaling Peptides and Proteins
RNA, Messenger
S100 Proteins
TRPV Cation Channels
TRPV6 protein, human
Tumor Suppressor Protein p53
Cyclin-Dependent Kinase Inhibitor p27
1-ethyl-2-benzimidazolinone
Calcium