Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
|
| pubmed:dateCreated |
1996-1-22
|
| pubmed:abstractText |
Increased expression of DNA topoisomerase II alpha has been associated with resistance to certain DNA-damaging alkylating agents, but no causal relationship or mechanism has been established. To investigate this observation, we developed a model of topoisomerase II overexpression by transfecting a full-length Chinese hamster ovary topoisomerase II alpha into EMT6 mouse mammary carcinoma. Topoisomerase II alpha-transfected cell lines demonstrated continued topoisomerase II alpha mRNA and protein expression, which were undetectable in vector-only lines, in stationary phase (G0-G1). The topoisomerase II transfectants were approximately 5-10-fold resistant to the alkylating agents cisplatin and mechlorethamine. Upon release from G0-G1, the topoisomerase II transfectants demonstrated more rapid thymidine incorporation and shorter cell-doubling times than control cells. Purified topoisomerase II and nuclear extracts with topoisomerase II-decatenating activity bound to cisplatin-treated DNA with significantly greater affinity than to untreated DNA in a cisplatin concentration-dependent manner. These observations suggest that expression of topoisomerase II alpha may have a role in cellular resistance to antineoplastic alkylating agents. The mechanism for this may involve increased binding of topoisomerase II alpha to alkylating agent-damaged DNA.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
55
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6109-16
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8521401-Animals,
pubmed-meshheading:8521401-Antineoplastic Agents, Alkylating,
pubmed-meshheading:8521401-Base Sequence,
pubmed-meshheading:8521401-CHO Cells,
pubmed-meshheading:8521401-Cisplatin,
pubmed-meshheading:8521401-Cricetinae,
pubmed-meshheading:8521401-DNA,
pubmed-meshheading:8521401-DNA Damage,
pubmed-meshheading:8521401-DNA Primers,
pubmed-meshheading:8521401-DNA Replication,
pubmed-meshheading:8521401-DNA Topoisomerases, Type II,
pubmed-meshheading:8521401-Drug Resistance, Neoplasm,
pubmed-meshheading:8521401-Gene Expression,
pubmed-meshheading:8521401-Mammary Neoplasms, Experimental,
pubmed-meshheading:8521401-Mice,
pubmed-meshheading:8521401-Molecular Sequence Data,
pubmed-meshheading:8521401-RNA, Messenger,
pubmed-meshheading:8521401-Transfection,
pubmed-meshheading:8521401-Tumor Cells, Cultured
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
DNA topoisomerase II alpha expression is associated with alkylating agent resistance.
|
| pubmed:affiliation |
Thorndike Laboratories, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|