Aurora kinases are essential for PKC-induced invasion and matrix metalloproteinase-9 expression in MCF-7 breast cancer cells.

Abstract

The Aurora kinase family of serine/threonine kinases are known to be crucial for cell cycle control. Aurora kinases are considered a target of anticancer drugs. However, few studies have assessed the effect of Aurora kinases in breast cancer. In the present study, to determine whether Aurora kinases play a role in oncogenic actions of protein kinase C (PKC), we investigated the effect of Aurora kinases on PKC-induced invasion and MMP-9 expression using breast cancer cells. Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the upregulation and phosphorylation of Aurora kinases via the MAPK signaling pathway. Moreover, the inhibition of Aurora kinases by their siRNAs and inhibitors suppressed TPA-induced cell invasion and expression of MMP-9 by inhibiting the activation of NF-κB/AP-1, major transcription factors for MMP-9 expression in MCF-7 cells. These results suggested that Aurora kinases mediate PKC-MAPK signal to NF-κB/AP-1 with increasing MMP-9 expression and invasion of MCF-7 cells. To the best of our knowledge, this is the first study to show that Aurora kinases are key molecules in PKC-induced invasion in breast cancer cells.

• Authors: Eun-Mi Noh, Young-Rae Lee, On-Yu Hong, Sung Hoo Jung, Hyun Jo Youn, Jong-Suk Kim
• Journal: Oncology reports (Oncol Rep) Vol. 34 Issue 2 Pg. 803-10 (Aug 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26044736 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Aurora Kinase A
• Aurora Kinase B
• Protein Kinase C
• Mitogen-Activated Protein Kinase Kinases
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Aurora Kinase A (biosynthesis, genetics)
• Aurora Kinase B (biosynthesis, genetics)
• Breast Neoplasms (genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 9 (biosynthesis, genetics)
• Mitogen-Activated Protein Kinase Kinases (genetics)
• NF-kappa B (biosynthesis, genetics)
• Neoplasm Invasiveness (genetics)
• Protein Kinase C (biosynthesis, genetics)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)