BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway

Schickling,Brandon M.; England,Sarah K.; Aykin-Burns,Nukhet; Norian,Lyse A.; Leslie,Kimberly K.; Frieden-Korovkina,Victoria P.

doi:10.3892/or.2014.3617

BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway

Authors:
- Brandon M. Schickling
- Sarah K. England
- Nukhet Aykin-Burns
- Lyse A. Norian
- Kimberly K. Leslie
- Victoria P. Frieden-Korovkina
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Affiliations: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA, Division of Basic Science Research, Washington University, St. Louis, MO, USA, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA, Department of Urology, University of Iowa, Iowa City, IA, USA
Published online on: November 24, 2014 https://doi.org/10.3892/or.2014.3617
Pages: 533-538
Copyright: © Schickling et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

In breast cancers, the large conductance Ca2+ and voltage sensitive K+ (BKCa) channels have been hypothesized to function as oncoproteins, yet it remains unclear how inhibition of channel activity impacts oncogenesis. We demonstrated herein that iberiotoxin (IbTX), an inhibitor of BKCa channels, differentially modulated the in vitro tumorigenic activities of hormone-independent breast cancer cells. Specifically, in HER-2/neu-overexpressing UACC893 cells and triple‑negative MDA-MB-231 cells, IbTX selectively attenuated anchorage-independent growth with concomitant downregulation of β-catenin as well as total and phosphorylated Akt and HER-2/neu. By contrast, HER-2/neu-overexpressing SK-BR-3 cells were insensitive to IbTX. Molecular analyses showed an absence of β-catenin and a dose-dependent upregulation of total and phosphorylated Akt and HER-2/neu in these cells. Taken together, these studies identify β-catenin as a putative modulator of the inhibitory actions of IbTX in sensitive breast cancer cells.

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