Silencing of casein kinase 2 inhibits pkc-induced cell invasion by targeting MMP-9 in MCF-7 cells

Abstract

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.