ETS ailesi transkripsiyon faktörü Elk-1'in kanser kök hücrelerindeki rolünün incelenmesi

According to the cancer stem cell theory, tumors have a subpopulation of cells that have the capacity for self-renewal and differentiation. These group of cells, namely cancer stem cells (CSCs), share some properties of normal stem cells. The dysregulation of specific signaling pathways and changes in downstream gene expression can cause failure in the regulation of stemness properties of stem cells, eventually causing tumorigenesis. There exists a complex interplay at both transcriptional and translational levels in the ultimate decision a stem cell or in this case a brain tumor-initiating cell (BTIC) to either keep itself as a stem cell (self-renewal) or become a specific cell through differentiation. The ETS family of transcription factors is one of the largest well-conserved transcription factor families. Elk-1, a TCF subfamily member, regulates many critical processes within the cell including apoptosis, tumorigenesis, and proliferation within the body. Elk-1 regulates neuronal survival and is neuroprotective; however, its survival-related transcriptional targets in neurons have not entirely identified yet. Together with the results of a former microarray conducted in the AxanLab, this led to the hypothesis that Elk-1 transcription factor may also be functional in regulating stemness genes and supporting their proliferation/self-renewal/survival in BTICs. In this study, CD133, a CSC marker, was used for the isolation of BTICs through positive selection. To find out the role of Elk-1, CD133+ BTICs were isolated, characterized, the effect of Elk-1 expression on the expression of various genes including the leading group of stemness genes, self-renewal, and proliferation in both normoxia and hypoxia were evaluated. The putative role of Elk-1 on the activity of selected promoters, namely SOX2, NANOG, and POU5F1, were assessed and the potential Elk-1 occupancy on several promoters were checked. Elk-1 roles in the regulation of the stemness gene promoters. The control over BTICs is not direct, but a rather complex mechanism is present. Finding out the role of Elk-1 from which the CSCs evade the regulations and the possible ways to overcome the progression of cancer can be the key for anti-cancer therapies.