title: BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway.
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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Schickling
authors.affiliation: Division of Basic Science Research, Washington University, St. Louis, MO, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: England
authors.affiliation: Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Nukhet
authors.initials: N
authors.lastname: Aykin-Burns
authors.affiliation: Department of Urology, University of Iowa, Iowa City, IA, USA.
authors.forename: Lyse A
authors.initials: LA
authors.lastname: Norian
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Frieden-Korovkina
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D010455:Peptides; D051176:beta Catenin; C064719:iberiotoxin