Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 168949, 11 pages
http://dx.doi.org/10.1155/2014/168949
Research Article

Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells

1Division of Pulmonary and Critical Care Medicine, China Medical University and Hospital, Taichung 404, Taiwan
2Department of Internal Medicine, China Medical University and Hospital, Taichung 404, Taiwan
3School of Medicine, China Medical University, Taichung 404, Taiwan
4Department of Life Science, National Chung-Hsing University, Taichung 402, Taiwan
5Department of Respiratory Therapy, China Medical University, Taichung 404, Taiwan
6Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan
7Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan
8Center for Molecular Medicine, China Medical University and Hospital, Taichung 404, Taiwan
9Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 106, Taiwan
10Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan
11Section of Breast Surgery, China Medical University and Hospital, Taichung 404, Taiwan
12Department of Surgery, China Medical University and Hospital, Taichung 404, Taiwan
13Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan
14Department of Biological Science & Technology, I-Shou University, Kaohsiung 824, Taiwan
15The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan
16Department of Biotechnology, Asia University, Taichung 413, Taiwan

Received 11 November 2013; Revised 4 January 2014; Accepted 6 January 2014; Published 23 February 2014

Academic Editor: Po-Lin Kuo

Copyright © 2014 Chih-Yen Tu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negative breast cancer cells more metastatic, suggesting a limitation to the therapeutic effectiveness of this dual inhibitor in HER2-heterogeneous tumors. Therefore, targeting EGFR expression may be a feasible approach to improve the anticancer efficiency of lapatinib-based therapy. Inhibition of HDAC has been previously reported to epigenetically suppress EGFR protein expression. In this study, however, our data indicated that treatment with HDAC inhibitors trichostatin A (TSA), but not suberoylanilide hydroxamic acid (SAHA) or HDAC siRNA, can attenuate both protein and mRNA expressions of EGFR in lapatinib-treated triple-negative breast cancer cells, suggesting that TSA may suppress EGFR expression independently of HDAC inhibition. Nevertheless, TSA reduced EGFR 3′UTR activity and induced the gene expression of microRNA-7, a known EGFR-targeting microRNA. Furthermore, treatment with microRNA-7 inhibitor attenuated TSA-mediated EGFR suppression. These results suggest that TSA induced microRNA-7 expression to downregulate EGFR expression in an HDAC-independent manner.