Inhibition by Imatinib of Expression of O-glycan-related Glycosyltransferases and Tumor-associated Carbohydrate Antigens in the K562 Human Leukemia Cell Line

Abstract

<br /><strong>Objective</strong>: To study changes of tumor associated carbohydrate antigen (TACAs) expression and mRNA levelsfor tumor associated glycosyltransferases, and assess subcellular localizations of N-acetyl galactosyltransferases(GalNAc-Ts) in the K562 leukemia cell line after imatinib treatment. <br /><strong>Methods</strong>: RT-PCR was performed toanalyze the expression of glycosyltransferases which synthesize O-glycan in tumor-associated carbohydrateantigens (TCTAs). The expression of Tn antigen, T antigen and sialyl T antigen on K562 cell membraneswas measured by flow cytometry after treatment with different concentrations of imatinib. Co-localization ofGalNAc-Ts and ER (endoplasmic reticulum) was determined by confocal laser scanning microcopy. <br /><strong>Results</strong>:Transcript expression levels of several glycosyltransferases related to TCTAs were decreased after imatinib(0-0.3μM) treatment. Expression of Tn antigen and T antigen was increased while that of sialyl T antigen wasdecreased. Co-localization of GalNAc-Ts and ER was reduced by 0.2μM of imatinib. <br /><strong>Conclusion</strong>: Imatinibinhibited the expression of O-glycan related TACAs and several related glycosyltransferases, while decreasingthe co-localization of GalNAc-Ts and ER and normalizing O-glycosylation in the K562 human leukemia cell.