Wang Yang, Xing Haiyan, Tian Zheng, Tang Kejing, Wang Jiying, Xu Zhifang, Rao Qing, Wang Min, Wang Jianxiang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, PR China.
Biochem Biophys Res Commun. 2009 Jul 3;384(3):341-6. doi: 10.1016/j.bbrc.2009.04.119. Epub 2009 May 4.
Midkine (MK), a heparin-binding growth factor, has been reported to be overexpressed in a variety of human solid tumors. In the previous study, we found that MK was overexpressed in bone marrow samples derived from acute leukemia (AL) patients. To elucidate the role of MK, we stably transfected MK in IL-3-dependent BA/F3 cells. The results indicated that the capacity of proliferation and colony formation was significantly increased in the MK-transfected subclones than in the empty vector-transfected subclones. MK potentiated proliferation of BA/F3 cells by promoting cell cycle progression. Apoptosis assays showed a remarkable reduction of apoptosis in MK expressing subclones. Exogenous MK could induce the phosphorylation of Raf-1, and inhibit the expression of Bax in BA/F3 cells. These results indicate that MK might be involved in the pathogenesis of leukemia and could be taken as an ideal diagnostic marker and molecular target for the treatment of acute leukemia.
中期因子（MK）是一种肝素结合生长因子，据报道在多种人类实体瘤中过度表达。在先前的研究中，我们发现MK在急性白血病（AL）患者的骨髓样本中过度表达。为了阐明MK的作用，我们在依赖白细胞介素-3的BA/F3细胞中稳定转染了MK。结果表明，与空载体转染的亚克隆相比，MK转染的亚克隆的增殖和集落形成能力显著增强。MK通过促进细胞周期进程增强BA/F3细胞的增殖。凋亡分析显示，表达MK的亚克隆中的凋亡显著减少。外源性MK可诱导BA/F3细胞中Raf-1的磷酸化，并抑制Bax的表达。这些结果表明，MK可能参与白血病的发病机制，可作为急性白血病理想的诊断标志物和治疗的分子靶点。
