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Epigenetic modification of DNA of tumor cell lines in normoxia and hypoxia
Omaňa Gudiňo, Žaneta ; Poljaková, Jitka (advisor) ; Hinďoš Hřebačková, Jana (referee)
5 Abstract Neuroblastoma is one of the most common cancer diseases diagnosed in children. This rapidly growing solid tumor is usually formed by hypoxic areas which arise as a consequence of inefficient and disorganized neovascularization. The cells stressed by hypoxia triggers transcription of many genes necessary for their survival, and conversely stop the production of proteins which are not necessarily needed for the survival in these severe conditions. The adaptation of cells to hypoxic conditions may appear due to the epigenetic regulation of metabolism associated with chromatin remodeling which involves the DNA methylation and also the posttranslational modifications of histones. Among the most important of these, there is the acetylation of lysine residues of histones associated with the DNA strands loosening, facilitated binding of transcription factors and the activation of gene expression. Thus, the first part of this study is concerned with changes in the acetylation of histones H3 and H4 of human neuroblastoma cell lines UKF-NB-3, UKF-NB-4, SH-SY5Y and SK-N-AS, cultured in parallel under standard culture conditions and in the absence of oxygen (hypoxia, 1% O2) for 24 hours, which are studied by Western blot analysis. Thereupon, the activity of histone deacetylases and histonacetyltransferases,...
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