Down-Regulation of Ca(2+)-Activated K⁺ Channel K(Ca)1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists.
Down-Regulation of Ca(2+)-Activated K⁺ Channel K(Ca)1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists.
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DOI：
10.3390/ijms17122083
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发表时间：
2016-12-11
影响因子：
5.6
通讯作者：
Ohya S
中科院分区：
文献类型：
--
作者：
Khatun A;Fujimoto M;Kito H;Niwa S;Suzuki T;Ohya S
维生素D （VD）可降低患乳腺癌的风险，改善疾病预后。潜在的VD类似物正在被开发作为乳腺癌治疗的治疗剂。大电导Ca2+激活的K+通道KCa1.1调节细胞内Ca2+信号通路，并与高级别肿瘤和不良预后相关。在本研究中，我们使用实时PCR、Western blotting、流式细胞术和电压敏感染料成像技术检测了VD受体（VDR）激动剂对人乳腺癌MDA-MB-453细胞中KCa1.1表达和活性的影响。用VDR激动剂处理72小时，可显著降低MDA-MB-453细胞中KCa1.1转录本和蛋白的表达水平，从而显著抑制特异性KCa1.1阻滞剂paxilline诱导的去极化反应。特异性蛋白酶体抑制剂MG132抑制VDR激动剂诱导的KCa1.1蛋白表达的降低。这些结果表明，KCa1.1是VDR信号的一个新的下游靶点，通过KCa1.1的转录抑制和KCa1.1蛋白降解的增强来下调KCa1.1，至少在一定程度上有助于VDR激动剂在乳腺癌细胞中的抗增殖作用。
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.
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影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
影响因子：
5.6
作者：
Marcinkowska E;Wallace GR;Brown G
通讯作者：
Brown G
影响因子：
3.7
作者：
Fu B;Wang H;Wang J;Barouhas I;Liu W;Shuboy A;Bushinsky DA;Zhou D;Favus MJ
通讯作者：
Favus MJ
影响因子：
2.9
作者：
Jose Gonzalez-Duarte, Ramiro;Cazares-Ordonez, Verna;Avila, Euclides
通讯作者：
Avila, Euclides
维生素D模拟MART-10减弱了三层阴性乳腺癌细胞的转移性潜力。
影响因子：
5.6
作者：
Chiang KC;Yeh TS;Chen SC;Pang JH;Yeh CN;Hsu JT;Chen LW;Kuo SF;Takano M;Kittaka A;Chen TC;Sun CC;Juang HH
通讯作者：
Juang HH