Global and gene specific DNA methylation in breast cancer cells was not affected during epithelial-to-mesenchymal transition in vitro
| Autor: | Naouale El Yamani, Lucia Kucerova, Viera Horvathova Kajabova, Svetlana Miklikova, Tomas Krivulcik, Iveta Zmetakova, Miroslava Matuskova, Bozena Smolkova, Zduriencikova M, Lenka Kalinkova, Maria Dusinska, Ivana Fridrichova, Andrea Babelova |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
Epithelial-Mesenchymal Transition Metal Nanoparticles Breast Neoplasms 02 engineering and technology Biology 01 natural sciences Epigenesis Genetic Cell Line Tumor Gene expression Humans Epithelial–mesenchymal transition Epigenetics Autocrine signalling Gene 010401 analytical chemistry Mesenchymal stem cell DNA Methylation 021001 nanoscience & nanotechnology Molecular biology 0104 chemical sciences Oncology Cell culture embryonic structures DNA methylation Cancer research Female Gold 0210 nano-technology |
| Zdroj: | Neoplasma (Bratislava) |
| Popis: | Epithelial-to-mesenchymal transition (EMT) significantly affects the risk of metastasising in breast cancer. Plasticity and reversibility of EMT suggest that epigenetic mechanisms could be the key drivers of these processes, but little is known about the dynamics of EMT-related epigenetic alterations. We hypothesised that EMT, mediated by autocrine and paracrine signals, will be accompanied by changes in DNA methylation profiles. Therefore, conditioned medium from adipose tissue-derived mesenchymal stromal cells was used for induction of EMT in human breast cancer SK-BR-3 cell line. EMT-related morphological alterations and changes in gene expression of EMT-associated markers were assessed. To reverse EMT, 20 nm size gold nanoparticles (AuNPs) synthesized by the citrate reduction method were applied. Finally, DNA methylation of LINE-1 sequences and promoter methylation of TIMP3, ADAM23 and BRMS1 genes were quantitatively evaluated by pyrosequencing. Despite the presence of EMT-associated morphological and gene expression changes in tumour cells, EMT induced by adipose tissue-derived mesenchymal stromal cells had almost no effect on LINE-1 and gene-specific DNA methylation patterns of TIMP3, ADAM23 and BRMS1 genes. Although treatment for 24, 48 or 72 hours with 20 nm AuNPs at a concentration of 3 µg/ml slightly decreased gene expression of EMT-associated markers in SK-BR-3 cells, it did not alter global or gene-specific DNA methylation. Our results suggest that changes in DNA methylation are not detectable in vitro in early phases of EMT. Previously published positive findings could represent rather the sustained presence of potent EMT-inducing signals or the synergistic effect of various epigenetic mechanisms. Treatment with AuNPs slightly attenuated EMT, and their therapeutic potential needs to be further investigated. |
| Databáze: | OpenAIRE |
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