Document Detail


Cytokine-induced restoration of differentiation and cell cycle arrest in v-Myc transformed U-937 monoblasts correlates with reduced Myc activity.
MedLine Citation:
PMID:  11236937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deregulated expression of the myc-family of oncogenes in hematopoietic and other cell types plays an important role in tumorigenesis, and results in increased proliferative potential and block of cellular differentiation. We have previously shown that IFN-gamma restores phorbol ester-induced differentiation and cell cycle arrest in v-myc transformed human U-937 monoblasts. To investigate whether other cytokine signals could also abrogate such a block, IL-1, IL-3, IL-4, IL-6, IL-7, IL-10, IL-11, LIF, oncostatin M, M-CSF, G-CSF and GM-CSF, and TGFbeta1, TNF-alpha, IFN-alpha were examined. We show that GM-CSF and IL-6, in combination with the phorbol ester 12-O-tetradecanoyl-phorbol acetate (TPA), restored differentiation and cell cycle arrest. In contrast, treatment by TGFbeta1 +/- TPA resulted in an efficient G1/G0 arrest, but did not appear to induce terminal differentiation. Restoration of differentiation and cell cycle arrest was accomplished despite maintained expression of the v-Myc protein. Our results show that the cytokine-induced signals reduced Myc-dependent transcription of an artificial target promoter/reporter gene construct, correlating in most, but not all, cases with decreased association of v- and c-Myc with its essential partner, Max. Thus, cytokine-induced signals may counteract the activity of deregulated Myc, and contribute to the normalization of differentiation, arrest in the G1/G0 phase of the cell cycle, or both.
Authors:
F Oberg; S Wu; F Bahram; K Nilsson; L G Larsson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Leukemia     Volume:  15     ISSN:  0887-6924     ISO Abbreviation:  Leukemia     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-09     Completed Date:  2001-03-29     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  217-27     Citation Subset:  IM    
Affiliation:
Department of Genetics and Pathology, University of Uppsala, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / physiology*
Cell Differentiation / drug effects,  physiology*
Cytokines / physiology*
Genes, myc*
Humans
Tetradecanoylphorbol Acetate / pharmacology
U937 Cells
Chemical
Reg. No./Substance:
0/Cytokines; 16561-29-8/Tetradecanoylphorbol Acetate

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