Linked Life Data

15093741

Source:http://linkedlifedata.com/resource/pubmed/id/15093741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-4-19
pubmed:abstractText
In this study we have investigated the role of topoisomerase (topo) IIalpha trafficking in cellular drug resistance. To accomplish this, it was necessary to separate the influence of cell cycle, drug uptake, topo protein levels, and enzyme trafficking on drug sensitivity. Thus, we developed a cell model (called accelerated plateau) using human myeloma H929 cells that reproducibly translocates topo IIalpha to the cytoplasm. Compared to log-phase cells, the cytoplasmic redistribution of topo IIalpha in plateau-phase cells correlated with a 10-fold resistance to VP-16 and a 40-60% reduction in the number of drug-induced double-strand DNA breaks. In addition, 7-fold more VP-16 was necessary to achieve 50% topo IIalpha band depletion, suggesting that there are fewer drug-induced topo-DNA complexes formed in quiescent cells than in log-phase cells. The total cellular amount of topo IIalpha and topo IIbeta protein in log- and plateau-phase cells was similar as determined by Western blot analysis. There was a 25% reduction in S-phase cell number in plateau cells (determined by bromodeoxyuridine (BrdU) incorporation), while there was no significant difference in the equilibrium concentrations of [(3)H]-VP-16 when log cells were compared with plateau cells. Furthermore, the nuclear/cytoplasmic ratio of topo IIalpha is increased 58-fold in accelerated-plateau H929 cells treated with leptomycin B (LMB) when compared to untreated cells. It appears that the nuclear-cytoplasmic shuttling of topo IIalpha, which decreases the amount of nuclear target enzyme, is a major mechanism of drug resistance to topo II inhibitors in plateau-phase myeloma cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
421-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15093741-Antibiotics, Antineoplastic, pubmed-meshheading:15093741-Antineoplastic Agents, pubmed-meshheading:15093741-Antineoplastic Agents, Phytogenic, pubmed-meshheading:15093741-Blotting, Western, pubmed-meshheading:15093741-Cell Line, Tumor, pubmed-meshheading:15093741-Cell Nucleus, pubmed-meshheading:15093741-Comet Assay, pubmed-meshheading:15093741-Cytoplasm, pubmed-meshheading:15093741-DNA Topoisomerases, Type II, pubmed-meshheading:15093741-Drug Resistance, Neoplasm, pubmed-meshheading:15093741-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:15093741-Etoposide, pubmed-meshheading:15093741-Fatty Acids, Unsaturated, pubmed-meshheading:15093741-Flow Cytometry, pubmed-meshheading:15093741-HL-60 Cells, pubmed-meshheading:15093741-Humans, pubmed-meshheading:15093741-Microscopy, Fluorescence, pubmed-meshheading:15093741-Mitoxantrone, pubmed-meshheading:15093741-Multiple Myeloma, pubmed-meshheading:15093741-Plasmacytoma, pubmed-meshheading:15093741-Protein Transport, pubmed-meshheading:15093741-Subcellular Fractions
pubmed:year
2004
pubmed:articleTitle
The cytoplasmic trafficking of DNA topoisomerase IIalpha correlates with etoposide resistance in human myeloma cells.
pubmed:affiliation
Experimental Therapeutics Program, Departments of Interdisciplinary Oncology and Biochemistry and Molecular Biology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.