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Role of cGAS-STING pathway in tumour suppression and tumorigenesis
Vasiľko, Marek ; Bruštíková, Kateřina (advisor) ; Číhařová, Barbora (referee)
The cGAS-STING immune pathway serves as a potent activator of type I immune response through the induction of IRF3 and NF-κB transcriptional pathways. It achieves activation via recognition of cytosolic DNA, regardless of its origin. Other than transcription pathways, it has also been observed to induce cell death and autophagy, along with inhibition of DNA damage repair. cGAS-STING is thus recognized as a crucial player in antiviral immunity; however, it is also known to play a role in cancer. Its relationship with cancer is described in a twofold manner, either as antitumoral,or tumour inducing. The manner of these interactions is yet unclear and warrants further study. This thesis provides a description of the cGAS-STING pathway, examples of both tumorigenesis and tumour suppression, along with a summary of its interactions with tumorigenic viruses. Key words: cGAS, STING, IRF3, NF-κB, tumour suppression, tumorigenesis, tumorigenic virus
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Role of heat shock proteins in the pathogenesis of leukaemia
Kopřivová, Olga ; Hromadníková, Ilona (advisor) ; Černá, Marie (referee)
(Abstract) Some of heat shock proteins (Hsp), for example the inducible form Hsp70, are expressed on the surface of tumour cells. High Hsp expression is reflected in tumour cell features, such as ability to progression, to metastasize and resistance to apoptosis. The question is whether Hsp gene expression correlates with surface expression. The aim of this master thesis is to compare surface and gene expression of Hsp70 and observe the gene expression of some other Hsp proteins (Hsp27, Hsp60, Hsp90 and HspBP1) in leukaemia. The research was carried out on cell lines obtained from leukaemic blasts of patients with acute myeloid leukaemia: UoC-M1, HL-60, OCI/AML3, THP-1, HU-3 and TF-1 that had been cultivated in vitro. Hsp70 surface expression was detected using flow cytometry, and gene expression of each Hsp was studied using real-time RT-PCR. It was found out that high surface expression of Hsp70 did not correlate with gene expression in consequence of negative feedback applied in Hsp expression regulation. Hsp27 gene expression was increased compared to negative (healthy) control on all tumour cell lines, with the highest increase on the THP-1 line. Hsp60 gene expression was increased compared to negative (healthy) control on all tumour cell lines and there were not remarkable differences in...
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Role of heat shock proteins in the pathogenesis of leukaemia
Kopřivová, Olga ; Hromadníková, Ilona (advisor) ; Černá, Marie (referee)
(Abstract) Some of heat shock proteins (Hsp), for example the inducible form Hsp70, are expressed on the surface of tumour cells. High Hsp expression is reflected in tumour cell features, such as ability to progression, to metastasize and resistance to apoptosis. The question is whether Hsp gene expression correlates with surface expression. The aim of this master thesis is to compare surface and gene expression of Hsp70 and observe the gene expression of some other Hsp proteins (Hsp27, Hsp60, Hsp90 and HspBP1) in leukaemia. The research was carried out on cell lines obtained from leukaemic blasts of patients with acute myeloid leukaemia: UoC-M1, HL-60, OCI/AML3, THP-1, HU-3 and TF-1 that had been cultivated in vitro. Hsp70 surface expression was detected using flow cytometry, and gene expression of each Hsp was studied using real-time RT-PCR. It was found out that high surface expression of Hsp70 did not correlate with gene expression in consequence of negative feedback applied in Hsp expression regulation. Hsp27 gene expression was increased compared to negative (healthy) control on all tumour cell lines, with the highest increase on the THP-1 line. Hsp60 gene expression was increased compared to negative (healthy) control on all tumour cell lines and there were not remarkable differences in...
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