EFFECT OF TLR9/AIM2 GENE KNOCKOUT IN MCF7 TUMOR CELLS ON ALTERATIONS OF OXIDATIVE STRESS AND HYPOXIA MARKER GENE EXPRESSION IN RESPONSE TO GC-ENRICHED DNA FRAGMENTS

The purpose of this study was to determine the influence of GC-DNA on the expression of hypoxia and oxidative stress marker genes in breast cancer MCF7 cells knocked out for the TLR9 and AIM2 encoding intracellular DNA sensor molecules. Material and methods. The study was conducted on intact MCF7 cells, four clones of MCF7 cells knocked out by the TLR9 gene (TLR9-/-), and two clones of MCF7 cells knocked out by the AIM2 gene (AIM2-/-). The protein expression was determined by flow cytofluorometry. The gene expression in cells was studied by real-time PCR.Results. The results of the study showed that knockout MCF7 cultures, in contrast to intact ones, respond to GC-DNA fragments stimulation by reducing the oxidative stress and hypoxia marker genes transcriptional activity both resulted in increased survival of cancer cells.Conclusions. The key role of TLR9 and AIM2 DNA sensors as triggers of adaptive survival-promoting responses of malignantcells to the CGDNA fragments originated from the tumor landscape has been proved.

GC-DNA, cell line MCF7, gene regulatory networks

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