Expression of Dlk1 gene in myelodysplastic syndrome determined by microarray, and its effects on leukemia cells.
Delta-like-1 (Dlk1, also Pref-1), a transmembrane and secreted protein, is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We found that the expression of Dlk1 was up-regulated in CD34+ cells from patients with myelodysplastic syndrome (MDS) by analyzing the gene expression profiles determined by microarray. The expression levels of Dlk1 mRNA frequently observed higher in the bone marrow mononuclear cells of MDS patients was confirmed by real-time RT-PCR. Forced expression of Dlk1 in transfected K562 cells enhanced proliferation, affected apoptosis induced by As2O3, and also influenced cell cycle induced by 12-O-tetra decanoylphorbol-acetate (TPA). By using the same experimental system we found that forced expression of Dlk1 increased the mRNA levels of HES1. It also inhibited p38 phosphorylation in transfected K562 cells treated with TPA. These results warrant further investigation of the role of Dlk1 in abnormal hematopoiesis in MDS.
Leukemia Research Division, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, First Affiliated Hospital, Soochow University, Suzhou, PR China.
Xiaofei
X
Qi
Zixing
Z
Chen
Dandan
D
Liu
Jiannong
J
Cen
Ming
M
Gu
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D018952:Antigens, CD34; D001152:Arsenicals; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010087:Oxides; D013755:Tetradecanoylphorbol Acetate; D000077237:Arsenic Trioxide