Expression analysis of Akirin-2, NFκB-p65 and β-catenin proteins in imatinib resistance of chronic myeloid leukemia.

Autor: Karabay AZ; a Faculty of Pharmacy, Department of Biochemistry , Ankara University , Ankara , Turkey., Koc A; a Faculty of Pharmacy, Department of Biochemistry , Ankara University , Ankara , Turkey., Ozkan T; b Faculty of Medicine, Department of Medical Biology , Ankara University , Ankara , Turkey., Hekmatshoar Y; b Faculty of Medicine, Department of Medical Biology , Ankara University , Ankara , Turkey., Altinok Gunes B; c Vocational School of Health , Ankara University , Ankara , Turkey., Sunguroglu A; b Faculty of Medicine, Department of Medical Biology , Ankara University , Ankara , Turkey., Buyukbingol Z; a Faculty of Pharmacy, Department of Biochemistry , Ankara University , Ankara , Turkey., Atalay A; d Biotechnology Institute, Ankara University , Ankara , Turkey., Aktan F; a Faculty of Pharmacy, Department of Biochemistry , Ankara University , Ankara , Turkey.
Jazyk: angličtina
Zdroj: Hematology (Amsterdam, Netherlands) [Hematology] 2018 Dec; Vol. 23 (10), pp. 765-770. Date of Electronic Publication: 2018 Jun 26.
DOI: 10.1080/10245332.2018.1488795
Abstrakt: Objective: Chronic myleoid leukemia (CML) is a myeloproliferative disorder characterized with the constitutive activation of Bcr-Abl tyrosine kinase which is a target for imatinib, the first line treatment option for CML. Constitutive activation of NFκB and β-catenin signaling promotes cellular proliferation and survival and resistance to Imatinib therapy in CML. Akirin-2 is a nuclear protein which is required for NFκB dependent gene expression as a cofactor and has been linked to Wnt/beta-catenin pathway. The purpose of this study is to examine Akirin-2, NFκB and β-catenin in imatinib resistance of CML and to test if any direct physical protein-protein interaction exists between NFkB and both β-catenin and Akirin-2.
Methods: RT-PCR and western blot were performed to determine Akirin-2, NFκB-p65 and β-catenin gene and protein expressions, Co-immunoprecipitation and chromatin immunoprecipitation analysis were carried out to detect the direct physical interactions and binding of NFκB-p65 and β-catenin proteins to MDR1 promoter region, respectively.
Results: β-catenin and NFκB-p65 proteins bound to DNA promoter regions of MDR1 in imatinib-sensitive and resistant CML cells, whereas any direct protein-protein interaction could not be found between NFκB-p65 and Akirin-2 or β-catenin proteins. Nuclear β-catenin and NFκB-p65 levels increased in imatinib resistance. Moreover, increased Akirin-2 protein accumulation in the nucleus was shown for the first time in imatinib resistant CML cells.
Discussion: We show for the first time that Akirin-2 can be a novel biomarker in imatinib resistance. Targeting Akirin-2, NFκB and β-catenin genes may provide an opportunity to overcome imatinib resistance in CML.
Databáze: MEDLINE
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