Document Detail

Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site-mediated translation via phosphatidylinositol 3-kinase pathway in human factor-dependent leukemic cells.
MedLine Citation:
PMID:  12855588     Owner:  NLM     Status:  MEDLINE    
To investigate the roles of c-myc during hematopoietic proliferation induced by growth factors, we used factor-dependent human leukemic cell lines (MO7e and F36P) in which proliferation, cell cycle progression, and c-Myc expression were strictly regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). In these cell lines, both c-myc mRNA and c-Myc protein stability were not affected by GM-CSF and IL-3, suggesting a regulation of c-Myc protein at the translational level. However, rapamycin, an inhibitor of cap-dependent translation, did not block c-myc induction by GM-CSF and IL-3. Thus, we studied the cap-independent translation, the internal ribosome entry site (IRES), during c-Myc protein synthesis using dicistronic reporter gene plasmids and found that GM-CSF and IL-3 activated c-myc IRES to initiate translation. c-myc IRES activation, c-Myc protein expression, and cell cycle progression were all blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In another factor-dependent cell line, UT7, we observed the cell cycle progression and up-regulation of c-Myc protein, c-myc mRNA, and c-myc IRES simultaneously, which were all inhibited by LY294002. Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells.
Norihiko Kobayashi; Kumiko Saeki; Akira Yuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-07-10
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-21     Completed Date:  2004-01-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3186-95     Citation Subset:  AIM; IM    
Department of Hematology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Cell Cycle / drug effects*
Cell Line, Tumor
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology,  physiology*
Growth Substances / pharmacology
Interleukin-3 / pharmacology,  physiology*
Leukemia / pathology*
Peptide Chain Initiation, Translational / drug effects
Protein Biosynthesis / drug effects*
Proto-Oncogene Proteins c-myc / biosynthesis*
RNA, Messenger / biosynthesis
Signal Transduction
Up-Regulation / drug effects
Reg. No./Substance:
0/Growth Substances; 0/Interleukin-3; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC 3-Kinase

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