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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-4-8
pubmed:abstractText
Characterizing genes associated with leukemic cell differentiation may provide help for understanding mechanisms on the leukemia differentiation. The aim of this study is to investigate whether the expression of melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) could be induced during leukemia differentiation and whether mda-7/IL-24 plays a role in leukemia differentiation. We showed that the expression of mda-7/IL-24 and IL-24 delE5, an mda-7/IL-24 splice variant, was induced in U937 and HL60 cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated monocytic differentiation. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway was required for their induction. Knockdown of mda-7/IL-24 and IL-24 delE5 resulted in significant inhibition of the monocytic differentiation induced by TPA. More importantly, ectopic overexpression of mda-7/IL-24 and IL-24 delE5 significantly induced U937 cells, HL60 cells, and blast cells from patients with acute myeloid leukemia-M5 to differentiate, whereas normal hematopoietic progenitors were not affected. Furthermore, the molecular effector associated with selective differentiation induction by mda-7/IL-24 and IL-24 delE5 may be reactive oxygen species (ROS), and the source of ROS generation was nicotinamide adenine dinucleotide phosphate oxidase. Taken together, our results reveal the mechanism by which TPA induces monocytic differentiation and show for the first time the specific differentiation-inducing effects of mda-7/IL-24 and IL-24 delE5 on human myeloid leukemic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1538-8514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
615-25
pubmed:meshHeading
pubmed-meshheading:21282359-Acute Disease, pubmed-meshheading:21282359-Alternative Splicing, pubmed-meshheading:21282359-Animals, pubmed-meshheading:21282359-Blotting, Western, pubmed-meshheading:21282359-Cell Differentiation, pubmed-meshheading:21282359-Enzyme Activation, pubmed-meshheading:21282359-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21282359-HL-60 Cells, pubmed-meshheading:21282359-Humans, pubmed-meshheading:21282359-Interleukins, pubmed-meshheading:21282359-Leukemia, Myeloid, pubmed-meshheading:21282359-Mice, pubmed-meshheading:21282359-Mice, Nude, pubmed-meshheading:21282359-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:21282359-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:21282359-Neoplasms, Experimental, pubmed-meshheading:21282359-Protein Isoforms, pubmed-meshheading:21282359-RNA Interference, pubmed-meshheading:21282359-Reactive Oxygen Species, pubmed-meshheading:21282359-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21282359-Tetradecanoylphorbol Acetate, pubmed-meshheading:21282359-Transplantation, Heterologous, pubmed-meshheading:21282359-Tumor Burden, pubmed-meshheading:21282359-U937 Cells
pubmed:year
2011
pubmed:articleTitle
Novel functions for mda-7/IL-24 and IL-24 delE5: regulation of differentiation of acute myeloid leukemic cells.
pubmed:affiliation
State Key Laboratory for Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't