Document Detail

Phorbol ester-induced monocytic differentiation is associated with G2 delay and down-regulation of cdc25 expression.
MedLine Citation:
PMID:  8466854     Owner:  NLM     Status:  MEDLINE    
Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with growth arrest and induction of monocytic differentiation. The present results demonstrate that exposure of G1- or S phase-enriched U-937 cells to TPA was associated with delayed transition through G2-M and then exit from the cell cycle in the subsequent G0-G1 phase. In contrast, G2-M cells treated with TPA progressed through G1-S, were delayed in the next G2-M phase, and then entered a nonproliferative G0-G1 state. The effects of TPA on expression of cell cycle control genes demonstrated down-regulation of the cdc25 mitotic inducer during S-G2 progression. In order to investigate the role of cdc25 in the control of cell cycle progression, U-937 cells were stably transfected with an antisense cdc25 construct under control of a metallothionein-inducible promoter. Expression of this construct in G1 phase cells was associated with a significant delay in transition through S and G2-M phase. Similar results were obtained when G1 phase cells were incubated with a 14-base pair antisense cdc25 oligomer. Taken together, these results indicate that the cdc25 gene product is functionally associated with S-G2 transition of proliferating myeloid leukemia cells and that down-regulation of this gene by TPA is associated with G2-M delay.
R Hass; H Gunji; M Hirano; R Weichselbaum; D Kufe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  4     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-05-11     Completed Date:  1993-05-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  159-66     Citation Subset:  IM    
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
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MeSH Terms
Base Sequence
Cell Differentiation / drug effects
Down-Regulation / drug effects
G2 Phase / drug effects*
Gene Expression / drug effects*
Leukemia, Myeloid / drug therapy*,  genetics
Molecular Sequence Data
Monocytes / cytology,  drug effects*
S Phase / drug effects*
Tetradecanoylphorbol Acetate / pharmacology*
Time Factors
Grant Support
Reg. No./Substance:
16561-29-8/Tetradecanoylphorbol Acetate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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