Effects of protein kinase Cdelta and phospholipase C-gamma1 on monocyte chemoattractant protein-1 expression in taxol-induced breast cancer cell death.
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 Cdelta (PKCdelta). In addition, taxol-induced MCP-1 expression was reduced by the ectopic expression of PKCdelta in a dose-dependent manner, indicating that PKCdelta 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-gamma1 increased the expression of MCP-1 in taxol-treated MCF-7 cells, indicating that PLC-gamma1 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.
Kim
Yoon Suk
YS
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 220-710, Korea.
An
Hyoung Tae
HT
Kim
Jeonghan
J
Ko
Jesang
J
D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D018932:Chemokine CCL2; D018925:Chemokines; D012333:RNA, Messenger; D051745:Protein Kinase C-delta; D051966:Phospholipase C gamma; D017239:Paclitaxel