Effects of protein kinase Cδ and phospholipase C-γ1 on monocyte chemoattractant protein-1 expression in taxol-induced breast cancer cell death

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that plays an important role in immune cell migration. It has been reported that chemokines, including MCP-1, are involved in angiogenesis and metastasis. However, the exact role of chemokines in cancer development is still obscure. We investigated the involvement of MCP-1 in taxol-induced breast cancer cell death. The anti-cancer drug taxol induced MCF-7 breast cancer cell death. Treatment with taxol increased the mRNA expression level of MCP-1 in a dose- and time-dependent manner. Up-regulation of MCP-1 by taxol was augmented in cells treated with rottlerin, a specific inhibitor of protein kinase Cδ (PKCδ). In addition, taxol-induced MCP-1 expression was reduced by the ectopic expression of PKCδ in a dose-dependent manner, indicating that PKCδ plays a negative role in taxol-induced MCP-1 expression in MCF-7 cells. On the other hand, taxol-induced up-regulation of MCP-1 was reduced in cells treated with U73122, an inhibitor of phospholipase C (PLC), and ectopic expression of PLC-γ1 increased the expression of MCP-1 in taxol-treated MCF-7 cells, indicating that PLC-γ1 functions as a positive regulator in taxol-induced MCP-1 expression. These results indicate that MCP-1 is involved in taxol-induced breast cancer cell death and we propose that taxol induces up-regulation of MCP-1 by affecting both positive and negative regulatory signaling pathways.