Down-Regulation of Ca-Activated K⁺ Channel K1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Dec 16

PMID 27973439

Citations 4

Authors

Anowara Khatun

Mayu Fujimoto

Hiroaki Kito

Satomi Niwa

Takayoshi Suzuki

Susumu Ohya

Affiliations

Soon will be listed here.

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 Ca-activated K⁺ channel K1.1 regulates intracellular Ca 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 K1.1 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 K1.1 transcripts and proteins in MDA-MB-453 cells, resulting in the significant inhibition of depolarization responses induced by paxilline, a specific K1.1 blocker. The specific proteasome inhibitor MG132 suppressed VDR agonist-induced decreases in K1.1 protein expression. These results suggest that K1.1 is a new downstream target of VDR signaling and the down-regulation of K1.1 through the transcriptional repression of K1.1 and enhancement of K1.1 protein degradation contribute, at least partly, to the antiproliferative effects of VDR agonists in breast cancer cells.

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