Linked Life Data

10739677

Source:http://linkedlifedata.com/resource/pubmed/id/10739677

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-5-12
pubmed:abstractText
In the present study, cross-drug resistance in multidrug-resistant (MDR) cells, which overexpress P-glycoprotein (Pgp), a mdr1 gene product, against Pgp-unrelated drugs, and its relevance to c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) activity were examined. The multidrug-resistant FM3A/M cells overexpressing Pgp were resistant to apoptotic cell death induced either by Pgp-related drugs including vincristine and vinblastine, which are pumped out by Pgp, or by the Pgp-unrelated drugs including 5'-fluorouracil (5-FU) and bleomycin, which are not targets for Pgp, compared with the parental FM3A cells. Verapamil reversed the resistance of FM3A/M cells to apoptosis induced by the Pgp-related drugs but not that induced by the Pgp-unrelated drugs. Interestingly, FM3A/M cells have shown significantly lower basal and drug-stimulated JNK/SAPK activities than FM3A cells. After transfection with pEBG-SEK or pEBG-SAPK constructs, FM3A/M cells recovered the basal and Pgp-unrelated drug-stimulated activities of JNK/SAPK and the susceptibility to Pgp-unrelated drug-induced apoptotic cell death comparable to those of FM3A cells. Furthermore, FM3A cells became resistant to apoptotic cell death induced by vincristine and 5-FU after transfection with pEBG-SEK(K --> R), a dominant negative inhibitory mutant of SEK. These results suggest that downregulation of JNK/SAPK activity appears to confer on Pgp-associated FM3A/M cells a cross-resistance to Pgp-unrelated drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
256
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
300-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10739677-Animals, pubmed-meshheading:10739677-Antineoplastic Agents, pubmed-meshheading:10739677-Apoptosis, pubmed-meshheading:10739677-Bleomycin, pubmed-meshheading:10739677-Cell Survival, pubmed-meshheading:10739677-Drug Resistance, Multiple, pubmed-meshheading:10739677-Female, pubmed-meshheading:10739677-Fluorouracil, pubmed-meshheading:10739677-Genes, MDR, pubmed-meshheading:10739677-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:10739677-Mammary Neoplasms, Experimental, pubmed-meshheading:10739677-Mice, pubmed-meshheading:10739677-Mitogen-Activated Protein Kinases, pubmed-meshheading:10739677-P-Glycoprotein, pubmed-meshheading:10739677-Recombinant Proteins, pubmed-meshheading:10739677-Transfection, pubmed-meshheading:10739677-Tumor Cells, Cultured, pubmed-meshheading:10739677-Verapamil, pubmed-meshheading:10739677-Vinblastine, pubmed-meshheading:10739677-Vincristine
pubmed:year
2000
pubmed:articleTitle
Downregulation of JNK/SAPK activity is associated with the cross-resistance to P-glycoprotein-unrelated drugs in multidrug-resistant FM3A/M cells overexpressing P-glycoprotein.
pubmed:affiliation
Department of Biochemistry, Pusan National University, Pusan, 602-739, Korea. kcdshbw@hyowon.pusan.ac.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't