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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Authors | Brandon M Schickling, Sarah K England, Nukhet Aykin-Burns, Lyse A Norian, Kimberly K Leslie, Victoria P Frieden-Korovkina |
Journal | Oncology reports
(Oncol Rep)
Vol. 33
Issue 2
Pg. 533-8
(Feb 2015)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 25422049
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- KCNMA1 protein, human
- Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
- Peptides
- beta Catenin
- iberiotoxin
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Topics |
- Antineoplastic Agents
(pharmacology)
- Breast Neoplasms
(genetics, metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
(antagonists & inhibitors, metabolism)
- Peptides
(pharmacology)
- Wnt Signaling Pathway
(drug effects)
- beta Catenin
(genetics, metabolism)
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