Document Detail


Detection of cell cycle- and differentiation stage-dependent human telomerase reverse transcriptase expression in single living cancer cells.
MedLine Citation:
PMID:  16584924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated telomerase activity is an important molecular signature of cancer cells and primitive cells in regenerative tissues. However, isolation of single living cells with endogenous telomerase activity has not yet been possible. Here, we developed adenovirus serotype 35 tropism-based vectors encoding destabilized enhanced green fluorescence protein with a half-life of 2 h (d2EGFP) driven by the human telomerase reverse transcriptase (hTERT) promoter. As assessed in telomerase-positive or -negative cell lines, the d2EGFP expression positively correlated with hTERT transcript content and telomerase activity. In retinoic acid-induced differentiating HL-60 cells, the d2EGFP expression is diminished in the same manner as the hTERT expression. Individual cells from HeLa and HL-60 cell lines exhibited heterogeneous d2EGFP expression, which was cell cycle dependent, as the sorted d2EGFP+ HL-60 cells contained twice as many cells in S/G2/M phase of the cell cycle compared with the d2EGFP- HL-60 cells. However, both cell populations exhibited the same proliferation and regeneration capacities. Heterogeneous d2EGFP expression was also detected in xenograft glioblastoma multiforme cells with tumor formation capacity. Thus, d2EGFP expression reported cell cycle- and differentiation stage-dependent hTERT expression. Our study facilitates isolation and characterization of single living cells with telomerase activity.
Authors:
Anna Edqvist; Johan Rebetz; Marcus Järås; Anna Rydelius; Gunnar Skagerberg; Leif G Salford; Bengt Widegren; Xiaolong Fan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-04-11
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  14     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-09-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  139-48     Citation Subset:  IM    
Affiliation:
Section of Immunology, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Cell Cycle / drug effects,  physiology*
Cell Differentiation / drug effects,  physiology*
Cell Line
Cell Line, Tumor
Cells, Cultured
DNA-Binding Proteins / genetics*,  metabolism
Gene Expression Regulation, Enzymologic
Gene Therapy / methods
Genetic Vectors / genetics
Green Fluorescent Proteins / genetics,  metabolism
HL-60 Cells
Hela Cells
Humans
K562 Cells
Mice
Mice, SCID
Models, Genetic
Neoplasms / genetics*,  pathology,  therapy
Promoter Regions, Genetic / genetics
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / genetics*,  metabolism
Tretinoin / pharmacology
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 147336-22-9/Green Fluorescent Proteins; 302-79-4/Tretinoin; EC 2.7.7.49/Telomerase

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


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