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Int. J. Mol. Sci. 2016, 17(12), 2083; doi:10.3390/ijms17122083

Down-Regulation of Ca2+-Activated K+ Channel KCa1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists

1
Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
2
Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 403-8334, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: ChulHee Kang
Received: 27 September 2016 / Revised: 1 December 2016 / Accepted: 8 December 2016 / Published: 11 December 2016
(This article belongs to the Special Issue Calcium Regulation and Sensing)
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Abstract

Vitamin D (VD) reduces the risk of breast cancer and improves disease prognoses. Potential VD analogs are being developed as therapeutic agents for breast cancer treatments. The large-conductance Ca2+-activated K+ channel KCa1.1 regulates intracellular Ca2+ signaling pathways and is associated with high grade tumors and poor prognoses. In the present study, we examined the effects of treatments with VD receptor (VDR) agonists on the expression and activity of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, flow cytometry, and voltage-sensitive dye imaging. Treatments with VDR agonists for 72 h markedly decreased the expression levels of KCa1.1 transcripts and proteins in MDA-MB-453 cells, resulting in the significant inhibition of depolarization responses induced by paxilline, a specific KCa1.1 blocker. The specific proteasome inhibitor MG132 suppressed VDR agonist-induced decreases in KCa1.1 protein expression. These results suggest that KCa1.1 is a new downstream target of VDR signaling and the down-regulation of KCa1.1 through the transcriptional repression of KCa1.1 and enhancement of KCa1.1 protein degradation contribute, at least partly, to the antiproliferative effects of VDR agonists in breast cancer cells. View Full-Text
Keywords: vitamin D receptor; breast cancer; KCa1.1; K+ channel; transcription; protein degradation vitamin D receptor; breast cancer; KCa1.1; K+ channel; transcription; protein degradation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Khatun, A.; Fujimoto, M.; Kito, H.; Niwa, S.; Suzuki, T.; Ohya, S. Down-Regulation of Ca2+-Activated K+ Channel KCa1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists. Int. J. Mol. Sci. 2016, 17, 2083.

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