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Aptamers affecting eIF4F subunits
Kopperová, Dana ; Feketová, Zuzana (advisor) ; Schierová, Michaela (referee)
Eukaryotic translation initiation factor 4F comprises of three subunits - eIF4A, eIF4G and eIF4E. These subunits play a key role in translation initiation. On its surface eIF4G binds other translation factors. eIF4A is RNA dependent helicase that is crucial for translation initiation. Affinity of eIF4E towards cap is enhanced if it is in complex with eIF4G. Specific molecules with high affinity were prepared by Selex. These molecules that bind various surfaces and different molecules in the cell are called aptamers. Aptamer binding eIF4A inhibits ATP hydrolysis. Activity of eIF4G may be affected by more aptamers but all resulting in translation inhibition. Aptamer binding eIF4E also inhibits translation by hindering cap binding. All of these translation factors may be detected in non-standard values in tumors. Aptamers against these proteins might bring a solution in the tumor treatment.
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Molecular mechanisms of the resistence of breast cancer cells to taxanes: the role of ABC transporters
Kopperová, Dana ; Kovář, Jan (advisor) ; Hrdý, Jiří (referee)
Resistance to chemotherapeutics is a widespread phenomenon in cancer cells that may counteract the successful therapy of many patients. In resistant cells, higher level of ABC transporters, among others, often can be detected. This high level of ABC transporters represents a suspected mechanism of acquired cancer resistance. We studied the molecular mechanism of resistance to taxanes in cancer cells using SK-BR-3 and MCF-7 breast cancer cell lines. We analyzed the effect of paclitaxel on apoptosis induction in the originally sensitive cells of these lines as compared to their counterpart resistant cells, developed by gradual adaptation to paclitaxel. In resistant cells of the SK-BR-3 and MCF-7 lines, we did not detected ongoing induction of apoptosis but we did detect significantly increased expression of ABCB1 transporter after paclitaxel application. By silencing the expression of the transport via employment of small interfering RNA (siRNA), we tested the role of the ABCB1 transporter in cells resistant to paclitaxel. We found that resistant cells with silenced expression of the ABCB1 transporter had a statistically significant increase of sensitivity to paclitaxel as compared to control resistant cells with high expression of this transporter. Along with increased sensitivity, we demonstrated...
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Aptamers affecting eIF4F subunits
Kopperová, Dana ; Schierová, Michaela (referee) ; Feketová, Zuzana (advisor)
Eukaryotic translation initiation factor 4F comprises of three subunits - eIF4A, eIF4G and eIF4E. These subunits play a key role in translation initiation. On its surface eIF4G binds other translation factors. eIF4A is RNA dependent helicase that is crucial for translation initiation. Affinity of eIF4E towards cap is enhanced if it is in complex with eIF4G. Specific molecules with high affinity were prepared by Selex. These molecules that bind various surfaces and different molecules in the cell are called aptamers. Aptamer binding eIF4A inhibits ATP hydrolysis. Activity of eIF4G may be affected by more aptamers but all resulting in translation inhibition. Aptamer binding eIF4E also inhibits translation by hindering cap binding. All of these translation factors may be detected in non-standard values in tumors. Aptamers against these proteins might bring a solution in the tumor treatment.
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