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Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
- Source :
- BioMed Research International, Vol 2014 (2014), BioMed Research International
- Publication Year :
- 2014
- Publisher :
- Hindawi Limited, 2014.
-
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.
- Subjects :
- Article Subject
medicine.drug_class
lcsh:Medicine
Antineoplastic Agents
Triple Negative Breast Neoplasms
Biology
Lapatinib
Hydroxamic Acids
General Biochemistry, Genetics and Molecular Biology
Tyrosine-kinase inhibitor
Histone Deacetylases
Downregulation and upregulation
Cell Line, Tumor
Gene expression
microRNA
medicine
Humans
RNA, Messenger
skin and connective tissue diseases
Protein Kinase Inhibitors
General Immunology and Microbiology
lcsh:R
General Medicine
MicroRNA 7
ErbB Receptors
Gene Expression Regulation, Neoplastic
MicroRNAs
Trichostatin A
Cancer research
Quinazolines
Tyrosine kinase
medicine.drug
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23146141 and 23146133
- Volume :
- 2014
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....8719b36a42e2bb10dc68dc99f851129b