Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry.
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.
Lallet-Daher
H
H
INSERM U800, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.
Roudbaraki
M
M
Bavencoffe
A
A
Mariot
P
P
Gackière
F
F
Bidaux
G
G
Urbain
R
R
Gosset
P
P
Delcourt
P
P
Fleurisse
L
L
Slomianny
C
C
Dewailly
E
E
Mauroy
B
B
Bonnal
J L
JL
Skryma
R
R
Prevarskaya
N
N
D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016193:G1 Phase; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000032:analysis / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D008564:Membrane Potentials; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis; D050916:TRPV Cation Channels / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D001562:Benzimidazoles; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D015220:Calcium Channels; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D009418:S100 Proteins; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; C102635:1-ethyl-2-benzimidazolinone; D002118:Calcium