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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-8-3
pubmed:abstractText
Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIa gene expression. Our previous studies have shown that transient transfection with a vector containing either Drosophila or human topoisomerase IIalpha gene into drug-resistant tumor cells enhanced their drug sensitivity. Furthermore, we constructed a recombinant adenovirus, Ad-hTopoIIalpha, containing the human topoisomerase IIa gene that was able to selectively increase etoposide sensitivity in drug-resistant tumor cells. We also examined Ad-hTopoIIalpha for therapeutic efficacy in vitro using additional etoposide-resistant cell lines, including a mouse breast cancer cell line and a human leukemia cell line. The etoposide-resistant mouse breast cancer cell line FvP, which is derived from FM3A, and etoposide-resistant human breast cancer cell line, MDA-VP, which derived from MDA-P cells showed increased sensitivity to etoposide as well as increased expression of human Topoisomerase IIa mRNA, but this was not seen in FM3A and MDA-P cells. On the other hand, the etoposide-resistant human leukemia cell line K562/MX2 and the parental cell line K562/P did not show enhanced sensitivity against etoposide or an increase in human Topoisomerase IIa mRNA. Using a recombinant adenovirus containing beta-galactosidase gene (Ad-beta-gal), K562 cells were not transducted by the recombinant adenovirus, while both etoposide-sensitive FM3A cells and etoposide resistant FvP cells were transducted by recombinant adenovirus. Ad-hTOP2alpha and etopside treatment showed reduced inoculated tumor weight in the mice. We concluded that a recombinant adenovirus containing the human Topoisomerase IIalpha gene might be a powerful tool for overcoming drug resistance in breast cancer cells, but not in leukemia cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0284-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
240-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16076696-Adenoviridae, pubmed-meshheading:16076696-Animals, pubmed-meshheading:16076696-Antigens, Neoplasm, pubmed-meshheading:16076696-Antineoplastic Agents, Phytogenic, pubmed-meshheading:16076696-Breast Neoplasms, pubmed-meshheading:16076696-Cell Line, Tumor, pubmed-meshheading:16076696-DNA Topoisomerases, Type II, pubmed-meshheading:16076696-DNA-Binding Proteins, pubmed-meshheading:16076696-Drug Resistance, Neoplasm, pubmed-meshheading:16076696-Etoposide, pubmed-meshheading:16076696-Female, pubmed-meshheading:16076696-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16076696-Gene Transfer Techniques, pubmed-meshheading:16076696-Genetic Vectors, pubmed-meshheading:16076696-Humans, pubmed-meshheading:16076696-Isoenzymes, pubmed-meshheading:16076696-Leukemia, pubmed-meshheading:16076696-Mammary Neoplasms, Experimental, pubmed-meshheading:16076696-Mice, pubmed-meshheading:16076696-Mice, Inbred BALB C, pubmed-meshheading:16076696-Mice, Inbred Strains, pubmed-meshheading:16076696-RNA, Messenger, pubmed-meshheading:16076696-Transduction, Genetic, pubmed-meshheading:16076696-Tumor Burden
pubmed:year
2005
pubmed:articleTitle
Adenovirus-mediated human topoisomerase IIalpha gene transfer increases the sensitivity of etoposide-resistant human and mouse breast cancer cells.
pubmed:affiliation
Department of Pediatrics, Nippon Medical School, Japan. VFF13540@nifty.ne.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't