Document Detail

1,25-dihydroxyvitamin D(3)-induced retardation of the G(2)/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells.
MedLine Citation:
PMID:  10502295     Owner:  NLM     Status:  MEDLINE    
Cellular differentiation of neoplastic cells after exposure to 1, 25-dihydroxyvitamin D(3) (1,25 D(3)) is accompanied by altered cell cycle regulation. In previous studies, blocks in both G(1)/S and G(2)/M checkpoints have been observed in 1,25D(3)-treated HL60 cells, but the mechanism of the 1,25D(3)-induced G(2)/M block has not been previously reported. In this study, we show by cell cycle analysis, using bromodeoxyuridine pulse-chase labeling, that the G(2)/M block in 1,25D(3)-treated HL60 cells is incomplete. We also demonstrate that although the 1,25D(3)-treated cells exhibit elevated levels of cyclin B1, Cdc25C, and Cdk7, which are positive regulators of the G(2)/M traverse, these cells have decreased protein levels of p34(cdc2) and decreased p34(cdc2) kinase activity. This provides potential mechanisms for the observed accumulation of cells in the G(2) cell cycle compartment and occasional polyploidization following treatment of HL60 cells with 1,25D(3). The data also suggest that the ability of some cells to traverse this block may be the result of cellular compensatory mechanisms responding to decreased p34(cdc2) activity by increasing the levels of other regulators of the G(2) traverse, such as cyclin B1, Cdc25C, and Cdk7.
L E Harrison; Q M Wang; G P Studzinski
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  75     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-11-22     Completed Date:  1999-11-22     Revised Date:  2012-06-08    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  226-34     Citation Subset:  IM    
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
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MeSH Terms
Bromodeoxyuridine / metabolism
CDC2 Protein Kinase / drug effects,  metabolism*
Calcitriol / pharmacology*
Cell Cycle Proteins / metabolism
Cell Death / drug effects
Cell Division / drug effects*
Cyclin B / metabolism
Cyclin B1
Cyclin-Dependent Kinases*
Flow Cytometry
G2 Phase / drug effects*
HL-60 Cells
Histones / metabolism
Mitosis / drug effects*
Models, Biological
Precipitin Tests
Protein-Serine-Threonine Kinases / metabolism
Time Factors
cdc25 Phosphatases / metabolism
Grant Support
R01-44722//PHS HHS
Reg. No./Substance:
0/CCNB1 protein, human; 0/Cell Cycle Proteins; 0/Cyclin B; 0/Cyclin B1; 0/Histones; 32222-06-3/Calcitriol; 59-14-3/Bromodeoxyuridine; EC Kinases; EC Protein Kinase; EC Kinases; EC kinase-activating kinase; EC protein, human; EC Phosphatases

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