School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia.
Pharmacology Unit, School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia.
Biometals. 2019 Dec;32(6):861-873. doi: 10.1007/s10534-019-00218-z. Epub 2019 Oct 3.
The intracellular zinc profiles of breast and prostate cancer cells are diametrically opposed, with hyper-accumulation of zinc in breast cancer, and low level in prostate cancer. This phenomenon is poorly understood. This study employs two breast and two prostate cancer cell lines to investigate the role of protein kinase CK2 in regulating zinc homeostasis. CK2 was targeted by its specific inhibitors 4,5,6,7-tetrabromobenzotriazole (TBB) and CX-4945, and by the specific siRNA against each of the three CK2 genes. The effect of zinc exposure after the above CK2 manipulation was observed by MTT [3-(4,5-dimethyliazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] cell viability assay and confocal microscopy for intracellular zinc level. The results demonstrate that CK2 is involved in regulating zinc homeostasis in breast and prostate cancer cells as both TBB and CX-4945 substantially decreased cell viability upon zinc exposure. siRNA-mediated knockdown of the three CK2 subunits (α, α' and β) revealed their discrete roles in regulating zinc homeostasis in breast and prostate cancer cells. Knockdown of CK2α' decreased the intracellular zinc level of breast cancer cells and in turn increased the cell viability while the opposite findings were obtained for the prostate cancer cells. Knockdown of CK2β expression substantially increased the zinc level in breast cancer cell lines whilst decreased the zinc level in prostate cancer cells. Taken together, this study shows that CK2 is involved in zinc homeostasis of breast and prostate cancer cells and opens a new avenue for research on these cancers.
乳腺癌和前列腺癌细胞的细胞内锌谱截然不同，乳腺癌细胞中锌的积累过度，而前列腺癌细胞中锌的水平较低。这种现象尚未得到很好的理解。本研究采用两种乳腺癌和两种前列腺癌细胞系，研究蛋白激酶 CK2 在调节锌稳态中的作用。CK2 被其特异性抑制剂 4,5,6,7-四溴苯并三唑（TBB）和 CX-4945 以及针对三个 CK2 基因中的每一个的特异性 siRNA 靶向。观察 CK2 处理后锌暴露对 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐]细胞活力测定和细胞内锌水平的共聚焦显微镜的影响。结果表明，CK2 参与调节乳腺癌和前列腺癌细胞的锌稳态，因为 TBB 和 CX-4945 在锌暴露后均显著降低细胞活力。三种 CK2 亚基（α、α'和β）的 siRNA 介导的敲低揭示了它们在调节乳腺癌和前列腺癌细胞的锌稳态中的离散作用。CK2α'的敲低降低了乳腺癌细胞的细胞内锌水平，从而增加了细胞活力，而前列腺癌细胞则得到了相反的结果。CK2β表达的敲低显著增加了乳腺癌细胞系中的锌水平，而降低了前列腺癌细胞中的锌水平。总之，这项研究表明 CK2 参与了乳腺癌和前列腺癌细胞的锌稳态，并为这些癌症的研究开辟了新途径。
