RT Journal Article
SR Electronic
T1 The Antiestrogen Tamoxifen Activates BK Channels and Stimulates Proliferation of MCF-7 Breast Cancer Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 843
OP 851
DO 10.1124/mol.106.028290
VO 71
IS 3
A1 Guyllaume Coiret
A1 Anne-Sophie Borowiec
A1 Pascal Mariot
A1 Halima Ouadid-Ahidouch
A1 Fabrice Matifat
YR 2007
UL http://molpharm.aspetjournals.org/content/71/3/843.abstract
AB In the present study, we investigated the effect of the antiestrogen compound tamoxifen on BK channels by the use of the patch-clamp technique. The perfusion of 10 nM tamoxifen significantly increased the magnitude of a voltage-dependent K+ current by 22.6 ± 10.6% (n = 23). The effect of tamoxifen was always obtained in the first minute, peaked at 5.9 ± 2.2 min (n = 23), and was abolished by the perfusion of tetraethylammonium (0.5 mM), charybdotoxin (50 nM), or iberiotoxin (100 nM). The stimulatory effect of 10 nM tamoxifen was the same at low (50 nM) and high (700 nM) internal calcium concentration and was not additive to that of 17-β-estradiol (E2) or its membrane-impermeant form, β-estradiol 6-(O-carboxymethyl)oxime:bovine serum albumin. Furthermore, the effect of tamoxifen was still recorded in the presence of the selective estrogen receptor antagonist faslodex (ICI-182,780; 1 μM). At the single-channel level, tamoxifen significantly increased the open probability of the BK channel by 46.2 ± 10.1% (n = 4) without changing its unitary conductance. Moreover, we show here that the stimulation of BK channel activity by tamoxifen is involved in MCF-7 cell proliferation. Taken together, these results permitted us to identify the BK channel as the molecular target of tamoxifen that probably acts at the same extracellular molecular level as E2. The site of action of tamoxifen is probably the channel itself or the auxiliary β subunits. The American Society for Pharmacology and Experimental Therapeutics