Linked Life Data

10606239

Source:http://linkedlifedata.com/resource/pubmed/id/10606239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2000-1-6
pubmed:abstractText
The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A family mRNAs. We thus conclude that colon and breast cancer cells have a capacity for glucuronidation that could contribute to intrinsic drug resistance in colon cancer cells and may be acquired in breast cancer cells. The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5938-46
pubmed:dateRevised
2007-9-25
pubmed:meshHeading
pubmed-meshheading:10606239-ATP-Binding Cassette Transporters, pubmed-meshheading:10606239-Antineoplastic Agents, pubmed-meshheading:10606239-Antineoplastic Agents, Phytogenic, pubmed-meshheading:10606239-Breast Neoplasms, pubmed-meshheading:10606239-Camptothecin, pubmed-meshheading:10606239-Cell Survival, pubmed-meshheading:10606239-DNA Damage, pubmed-meshheading:10606239-Drug Resistance, Multiple, pubmed-meshheading:10606239-Epirubicin, pubmed-meshheading:10606239-Female, pubmed-meshheading:10606239-Glucuronides, pubmed-meshheading:10606239-Glucuronosyltransferase, pubmed-meshheading:10606239-Humans, pubmed-meshheading:10606239-Microscopy, Confocal, pubmed-meshheading:10606239-Mitoxantrone, pubmed-meshheading:10606239-Polymerase Chain Reaction, pubmed-meshheading:10606239-Topotecan, pubmed-meshheading:10606239-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells.
pubmed:affiliation
Medicine Branch, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article