Document Detail


Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in HL60 cell variants.
MedLine Citation:
PMID:  9168815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Differentiation generally leads to cell cycle arrest. Human leukemia HL60 cells respond to the presence of 1,25-dihydroxyvitamin D3 (1,25D3) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle. We have recently reported a series (A) of 1,25D3-resistant variants of HL60 cells which proliferate in the presence of 1,25D3 and do not express differentiation markers (Exp. Cell Res. 224, 312, 1996). We now describe another series (B) of such variants, which differ from A series cells grown in similar concentrations of 1,25D3 in that they express the CD14 antigen and nonspecific esterase, characteristic of the monocyte, while continuing to proliferate and they develop hypotetraploid DNA (4C) content at higher concentrations of ambient 1,25D3 than the A series cells. Cells in the B series with 4C DNA content (100B and 200B) also differed from the A series 4C cells by the absence of DNA binding by the full-length Sp1 transcription factor. However, B series cells resembled the A series cells in exhibiting faster growth rates than the parental HL60 cells and showed high levels of vitamin D receptor and retinoid receptor X proteins. These results show that the initial steps in the 1,25D3 signaling pathway are intact in B series resistant cells and lead to the appearance of early markers of monocytic differentiation. However, the progression to subsequent events which comprise terminal differentiation and cell cycle arrest is halted during the adaptation to the presence of 1,25D3 in these cells. Thus, the availability of these variant cells should provide a system for studying the link between differentiation and cell cycle arrest.
Authors:
G P Studzinski; B Rathod; Q M Wang; J Rao; F Zhang
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  232     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-23     Completed Date:  1997-06-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  376-87     Citation Subset:  IM    
Affiliation:
Department of Pathology, UMD-New Jersey Medical School, Newark 07103, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD14 / biosynthesis
Antigens, Differentiation, Myelomonocytic / biosynthesis
Biological Markers
Calcitriol / pharmacology
Cell Cycle / drug effects
Cell Differentiation / drug effects
Cell Division / drug effects
DNA, Neoplasm / analysis
HL-60 Cells / cytology*,  drug effects
Humans
Male
Monocytes / cytology*
Neoplasm Proteins / analysis
Phosphopyruvate Hydratase / biosynthesis
Receptors, Calcitriol / analysis
Receptors, Retinoic Acid / analysis
Retinoid X Receptors
Sp1 Transcription Factor / metabolism
Transcription Factors / analysis
Grant Support
ID/Acronym/Agency:
R01-CA 44722/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/Antigens, Differentiation, Myelomonocytic; 0/Biological Markers; 0/DNA, Neoplasm; 0/Neoplasm Proteins; 0/Receptors, Calcitriol; 0/Receptors, Retinoic Acid; 0/Retinoid X Receptors; 0/Sp1 Transcription Factor; 0/Transcription Factors; 32222-06-3/Calcitriol; EC 4.2.1.11/Phosphopyruvate Hydratase

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