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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Schickling, BM; England, SK; Aykin-Burns, N; Norian, LA; Leslie, KK; Frieden-Korovkina, VP

Published Date

  • February 2015

Published In

Volume / Issue

  • 33 / 2

Start / End Page

  • 533 - 538

PubMed ID

  • 25422049

Pubmed Central ID

  • PMC4306270

Electronic International Standard Serial Number (EISSN)

  • 1791-2431

Digital Object Identifier (DOI)

  • 10.3892/or.2014.3617


  • eng

Conference Location

  • Greece