Synergistic effects of combined DNA methyltransferase inhibition and MBD2 depletion on breast cancer cells; MBD2 depletion blocks 5-aza-2'-deoxycytidine-triggered invasiveness
| Autor: | Moshe Szyf, Michael Hallett, Bishnu Bhattacharya, Chen Chen Li, Matthew Suderman, Ani Arakelian, Flora Chik, Shafaat A. Rabbani, David Cheishvili |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Methyltransferase Azacitidine Breast Neoplasms Original Manuscript Biology Decitabine DNA methyltransferase chemistry.chemical_compound medicine Gene silencing Humans Neoplasm Invasiveness Molecular Targeted Therapy Enzyme Inhibitors Promoter Regions Genetic Gene DNA Modification Methylases General Medicine DNA Methylation In vitro DNA-Binding Proteins Gene Expression Regulation Neoplastic chemistry DNA methylation Cancer research MCF-7 Cells Female DNA medicine.drug |
| Zdroj: | Carcinogenesis. 35(11) |
| ISSN: | 1460-2180 |
| Popis: | 5-Aza-2ʹ-deoxycytidine (5-azaCdR) not only inhibits growth of non-invasive breast cancer cells but also increases their invasiveness through induction of pro-metastatic genes. Methylated DNA binding protein 2 (MBD2) is involved in silencing methylated tumor suppressor genes as well as activation of pro-metastatic genes. In this study, we show that a combination of MBD2 depletion and DNA methyltransferases (DNMT) inhibition in breast cancer cells results in a combined effect in vitro and in vivo, enhancing tumor growth arrest on one hand, while inhibiting invasiveness triggered by 5-azaCdR on the other hand. The combined treatment of MBD2 depletion and 5-azaCdR suppresses and augments distinct gene networks that are induced by DNMT inhibition alone. These data point to a potential new approach in targeting the DNA methylation machinery by combination of MBD2 and DNMT inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|