The role of the tyrosine kinase Syk in retinoic acid-induced leukemic HL-60 cell differentiation

摘要

SYK encodes the tyrosine kinase protein belonging to the signal-transducing molecules that interact with activated immunoreceptors. The current evidence indicates that deregulated Syk is involved in the pathogenesis of cancer. One of the most promising anticancer therapy strategies is the induction of cell terminal differentiation. In promyelocytic HL-60 cells, retinoic acid (RA) induces differentiation towards granulocytes. Increase in the activity of Syk during the process of differentiation suggests that Syk might play a role in directing HL-60 cells towards granulocytic differentiation. Therefore, we have studied the involvement of Syk tyrosine kinase in the process of retinoic acid-induced granulocytic differentiation of HL-60 cells. The 2.6-kb human SYK cDNA fragment harboring a complete coding sequence was inserted into the pLXSN retroviral vector in sense and antisense orientation and transfected into HL-60 cells. Following RA treatment, HL-60 cells transfected with SYK showed an increased differentiation to granulocytes when compared with the control cells transfected with an empty pLXSN vector. Reduction of the intracellular Syk level by antisense or short interfering RNA (siRNA) strategy yielded the inhibition of HL-60 cell differentiation. We propose that Syk is a positive regulator of retinoic acid-induced granulocytic differentiation of leukemic HL-60 cells and presents a potential target for the development of new anticancer therapies.