Overexpression of Midkine promotes the viability of BA/F3 cells.
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.
Wang
Yang
Y
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.
Xing
Haiyan
H
Tian
Zheng
Z
Tang
Kejing
K
Wang
Jiying
J
Xu
Zhifang
Z
Rao
Qing
Q
Wang
Min
M
Wang
Jianxiang
J
D000328:Adult; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism
D014408:Biomarkers, Tumor; C066254:MDK protein, human; D009414:Nerve Growth Factors; D051028:bcl-2-Associated X Protein; D000078792:Midkine; D048490:raf Kinases