Linked Life Data

10796074

Source:http://linkedlifedata.com/resource/pubmed/id/10796074

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-5-12
pubmed:abstractText
A major obstacle for the effective treatment of cancer is the phenomenon of multidrug resistance (MDR) exhibited by many tumor cells. Many, but not all, MDR cells exhibit membrane-associated P-glycoprotein (P-gp), a drug efflux pump. However, most mechanisms of MDR are complex, employing P-gp in combination with other, ill-defined activities. Altered cytosolic pH (pHi) has been implicated to play a role in drug resistance. In the current study, we investigated mechanisms of pHi regulation in drug-sensitive (MCF-7/S) and drug-resistant human breast cancer cells. Of the drug-resistant lines, one contained P-gp (MCF-7/DOX; also referred to as MCF-7/D40) and one did not (MCF-7/MITOX). The resting steady-state pHi was similar in the three cell lines. In addition, in all the cell lines, HCO3- slightly acidified pHi and increased the rates of pHi recovery after an acid load, indicating the presence of anion exchanger (AE) activity. These data indicate that neither Na+/H+ exchange nor AE is differentially expressed in these cell lines. The presence of plasma membrane vacuolar-type H+-ATPase (pmV-ATPase) activity in these cell lines was then investigated. In the absence of Na+ and HCO3-, MCF-7/S cells did not recover from acid loads, whereas MCF-7/MITOX and MCF-7/DOX cells did. Furthermore, recovery of pHi was inhibited by bafilomycin A1 and NBD-Cl, potent V-ATPase inhibitors. Attempts to localize V-ATPase immunocytochemically at the plasma membranes of these cells were unsuccessful, indicating that V-ATPase is not statically resident at the plasma membrane. Consistent with this was the observation that release of endosomally trapped dextran was more rapid in the drug-resistant, compared with the drug-sensitive cells. Furthermore, the drug-resistant cells entrapped doxorubicin into intracellular vesicles whereas the drug-sensitive cells did not. Hence, it is hypothesized that the measured pmV-ATPase activity in the drug-resistant cells is a consequence of rapid endomembrane turnover. The potential impact of this behavior on drug resistance is examined in a companion manuscript.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1037-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10796074-Antineoplastic Agents, pubmed-meshheading:10796074-Benzopyrans, pubmed-meshheading:10796074-Bicarbonates, pubmed-meshheading:10796074-Biological Transport, pubmed-meshheading:10796074-Breast Neoplasms, pubmed-meshheading:10796074-Cell Compartmentation, pubmed-meshheading:10796074-Doxorubicin, pubmed-meshheading:10796074-Drug Resistance, Multiple, pubmed-meshheading:10796074-Drug Resistance, Neoplasm, pubmed-meshheading:10796074-Endosomes, pubmed-meshheading:10796074-Female, pubmed-meshheading:10796074-Fluorescent Dyes, pubmed-meshheading:10796074-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10796074-Humans, pubmed-meshheading:10796074-Hydrogen-Ion Concentration, pubmed-meshheading:10796074-Naphthols, pubmed-meshheading:10796074-Proton-Translocating ATPases, pubmed-meshheading:10796074-Rhodamines, pubmed-meshheading:10796074-Sodium-Hydrogen Antiporter, pubmed-meshheading:10796074-Tumor Cells, Cultured, pubmed-meshheading:10796074-Vacuolar Proton-Translocating ATPases, pubmed-meshheading:10796074-Vacuoles
pubmed:year
1999
pubmed:articleTitle
pH and drug resistance. I. Functional expression of plasmalemmal V-type H+-ATPase in drug-resistant human breast carcinoma cell lines.
pubmed:affiliation
Department of Biochemistry, University of Arizona Health Sciences Center, Tucson 85724-5042, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.