Akademik Veri Yönetim Sistemi
SERCAN H. O. (Yürütücü), Aydın B.
Yükseköğretim Kurumları Destekli Proje, BAP Araştırma Projesi, 2023 - 2025
The Wnt/ß-catenin signaling pathway is an evolutionarily conserved pathway that is the focus of research in embryogenic development, homeostasis and cancer biology. In the absence of Wnt ligan binding to the Frizzled receptor protein, the pathway becomes inactive and the ß-catenin degradation complex initiates the phosphorylation process that triggers the degradation of free β-catenin. Studies on Wnt/ß-catenin signaling pathway disorders in leukemias are available in the literature. Chronic myeloid leukemia (CML) is the first hematopoietic malignancy in which Wnt/ß-catenin signaling pathway dysregulation has been described. In vivo experiments have shown that leukemia progression is β-catenin dependent and loss of β-catenin attenuates Bcr-Abl-induced CML development. It suggests that Wnt/β-catenin signaling is important for maintaining Bcr-Abl protein at normal levels. The detection of Wnt/ß-catenin signaling pathway defects in CML suggests that this pathway plays an important role in the pathogenesis of the disease. Many factors that lead to an increase in intracellular ß-catenin levels may cause this pathway to become uncontrolled. Epigenetic silencing of Wnt/β-catenin negative regulatory proteins such as the sFRP family, of which sFRP1 is a member, is another mechanism. Within the scope of the proposed project, in vitro experiments to be carried out in the K562 cell line aim to determine the effect of sFRP1 protein on the expression of genes grouped as hematopoiesis, leukemia formation/development and stem cell-related genes in the cell. The K562 cell line is a blastic phase leukemia cell line that is epigenetically silenced in terms of the sFRP1 gene and lacks sFRP1 protein expression. In our laboratory, the K562 cell line was stably transfected with an expression vector containing the sFRP1 gene to create a form that continuously expresses sFRP1, which we define as K562s. The fact that the K562 cell, which we created within our own means and which continuously expresses sFRP1, will be used in the study does not contribute to the unique value of each data we will obtain from our project. After our project, mTOr increased 2.17-fold, PKC 1.35-fold, ß-TrCP 1.6-fold, Dvl2 2.9-fold, Dvl 3 1.95-fold. CK1e 0.98-fold, BRD7 0.41-fold, rhoA 0.32-fold, CamKII 0.81-fold, Dvl1 0.66-fold and rUNx2 0.29-fold.
We think that the main mechanism of protein increase and decrease is more related to the processes in the cell in which feedback mechanisms act. With the findings from this study, we plan to conduct more specific studies on the genes in which we detected changes. The data we have obtained have been very valuable in creating new projects.