Received for publication June 30, 2006.
Revised December 12, 2006.
Accepted for publication December 12, 2006.

The antiestrogen tamoxifen activates BK channels and stimulates proliferation of MCF-7 breast cancer cells

Abstract

In the present study, we have 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 TEA (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 E₂ or its membrane impermeant form E₂BSA. Furthermore, the effect of tamoxifen was still recorded in the presence of the selective estrogen receptor (ER) antagonist ICI 182,780 (1 µM). At the single channel level, tamoxifen significantly increased NPo 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 subunits.

Key words: Ion channel regulation, Sex hormones, Potassium, Membrane targets

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