Abstract P5-07-04: Aurora kinase regulates PKC-mediated MMP-9 expression and invasion in MCF-7 breast cancer cells

Aurora kinase is a novel family of serine/threonine kinases. Elevated expression of aurora kinase A and B is observed in many tumor cells, and dysregulation of aurora kinase has been linked to tumorigenesis. Therefore, a number of studies focused in their oncogene activities as anti-tumor targets. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM) and it is important process for breast cancer cell invasion. MMP-9 can be stimulated by activation of various cellular signaling pathways including protein kinase C (PKC), and mitogen-activated protein kinase (MAPKs), activator protein-1 (AP-1) and nuclear factor-kappaB (NF-κB) signaling pathways. Here, we show that 12-O-tetradecanoylphorbol-13-acetate (TPA), a directly PKC activator stimulation resulted in an up-regulation and phosphorlyation of aurora kinases in MCF-7 breast cancer cells. Also, Results showed that inhibition of the aurora kinases suppressed TPA-induced MMP-9 secretion/expression and cell invasion through suppression of NF-κB, AP-1, and MAPKs in MCF-7 breast cancer cell. In conclusion, this study provides new insight into the novel role of aurora kinase for expression of MMP-9 by TPA and regulation of aurora kinase by TPA through MAPKs signaling pathway. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-07-04.