Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeollabuk 570‑749, Republic of Korea.
Department of Oral Biochemistry, School of Dentistry, Wonkwang University, Iksan, Jeollabuk 570‑749, Republic of Korea.
Mol Med Rep. 2018 Jun;17(6):8397-8402. doi: 10.3892/mmr.2018.8885. Epub 2018 Apr 13.
Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase‑9 (MMP‑9) via nuclear factor‑κB (NF‑κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF‑7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP‑9 in MCF‑7 cells were investigated using reverse transcription‑quantitative polymerase chain reaction, western blot analyses and a zymography assay. Cell invasiveness was investigated using a Matrigel invasion assay, and it was revealed that small interfering RNA specific for CK2 suppressed PKC induced cell invasion by regulating MMP‑9 expression via activation of the p38 kinase/c‑Jun N‑terminal kinase/NF‑κB pathway. In addition, it was demonstrated that CK2 inhibitors [apigenin (20 µM), emodin (20 µM) or 2‑dimethylamino‑4,5,6,7‑tetrabromo‑1H‑benzimidazole (2 µM)] suppressed PKC induced cell invasion and MMP‑9 expression. The results of the present study suggested that CK2 is an important factor involved in the induction of MCF‑7 breast cancer cell invasion by PKC. Therefore, CK2 may represent novel candidates for therapy intended to inhibit invasion in breast cancer.
酪蛋白激酶 2（CK2）是一种丝氨酸/苏氨酸蛋白激酶，被认为是乳腺肿瘤发生的重要因素。已经证明，通过核因子-κB（NF-κB）激活增加基质金属蛋白酶-9（MMP-9）的表达可促进乳腺癌细胞侵袭。在本研究中，研究了 CK2 参与蛋白激酶 C（PKC）诱导 MCF-7 乳腺癌细胞侵袭的情况以及潜在的分子机制。使用逆转录-定量聚合酶链反应、western blot 分析和酶谱分析研究 MCF-7 细胞中 MMP-9 的 mRNA 和蛋白水平。使用 Matrigel 侵袭测定法研究细胞侵袭性，结果表明，针对 CK2 的小干扰 RNA 通过激活 p38 激酶/c-Jun N-末端激酶/NF-κB 通路调节 MMP-9 表达，抑制 PKC 诱导的细胞侵袭。此外，还表明 CK2 抑制剂[芹菜素（20 μM）、大黄素（20 μM）或 2-二甲基氨基-4,5,6,7-四溴-1H-苯并咪唑（2 μM）]抑制 PKC 诱导的细胞侵袭和 MMP-9 表达。本研究的结果表明，CK2 是 PKC 诱导 MCF-7 乳腺癌细胞侵袭的重要因素。因此，CK2 可能代表用于抑制乳腺癌侵袭的新型治疗候选物。
