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BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway
In breast cancers, the large conductance Ca(2+) 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,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306270/ https://www.ncbi.nlm.nih.gov/pubmed/25422049 http://dx.doi.org/10.3892/or.2014.3617 |
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author | SCHICKLING, BRANDON M. ENGLAND, SARAH K. AYKIN-BURNS, NUKHET NORIAN, LYSE A. LESLIE, KIMBERLY K. FRIEDEN-KOROVKINA, VICTORIA P. |
author_facet | SCHICKLING, BRANDON M. ENGLAND, SARAH K. AYKIN-BURNS, NUKHET NORIAN, LYSE A. LESLIE, KIMBERLY K. FRIEDEN-KOROVKINA, VICTORIA P. |
author_sort | SCHICKLING, BRANDON M. |
collection | PubMed |
description | In breast cancers, the large conductance Ca(2+) 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. |
format | Online Article Text |
id | pubmed-4306270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-43062702015-01-27 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. Oncol Rep Articles In breast cancers, the large conductance Ca(2+) 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. D.A. Spandidos 2015-02 2014-11-24 /pmc/articles/PMC4306270/ /pubmed/25422049 http://dx.doi.org/10.3892/or.2014.3617 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles SCHICKLING, BRANDON M. ENGLAND, SARAH K. AYKIN-BURNS, NUKHET NORIAN, LYSE A. LESLIE, KIMBERLY K. FRIEDEN-KOROVKINA, VICTORIA P. BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title | BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title_full | BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title_fullStr | BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title_full_unstemmed | BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title_short | BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway |
title_sort | bkca channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the wnt pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306270/ https://www.ncbi.nlm.nih.gov/pubmed/25422049 http://dx.doi.org/10.3892/or.2014.3617 |
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