Linked Life Data

9506534

Source:http://linkedlifedata.com/resource/pubmed/id/9506534

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-3-24
pubmed:abstractText
The intracellular location of the MDR1 gene product, known as P-glycoprotein (P-gp), has been detected by flow cytometry in 3 stabilized human melanoma cell lines which had never undergone cytotoxic drug treatment and did not express P-gp on the plasma membrane. In addition, MDR1 mRNA expression was revealed by RT-PCR in the same cell lines. Immunofluorescence microscopy, performed by using the same 2 monoclonal antibodies (MM4.17 and MRK-16) as employed in the flow-cytometric analysis, revealed the presence of P-gp intracytoplasmically, in a well-defined perinuclear region. Double immunofluorescence labelling and immunoelectron microscopy strongly suggested the location of the transporter molecule in the Golgi apparatus. The same observations have been obtained on a primary culture from a metastasis of human melanoma. Analysis of the expression of another membrane transport protein, the multidrug-resistance-related protein (MRP1), showed that it was present in the cytoplasm of all the melanoma cell lines examined. MRP1 also showed Golgi-like localization. The study by laser scanning confocal microscopy on the intracellular localization of the anti-tumoral agent doxorubicin (DOX) during the drug-uptake and -efflux phases, indicated the Golgi apparatus as a preferential accumulation site for the anthracyclinic antibiotic. P-gp function modulators (verapamil and cyclosporin A) were able to modify DOX intracytoplasmic distribution and to increase drug intracellular concentration and cytotoxic effect in melanoma cells. On the contrary, MRP1 modulators (probenecid and genistein) did not significantly influence either DOX efflux and distribution or the sensitivity of melanoma cells to the cytotoxic drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
885-93
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:9506534-Biological Transport, pubmed-meshheading:9506534-Cell Compartmentation, pubmed-meshheading:9506534-Cells, Cultured, pubmed-meshheading:9506534-Cyclosporine, pubmed-meshheading:9506534-DNA-Binding Proteins, pubmed-meshheading:9506534-Doxorubicin, pubmed-meshheading:9506534-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:9506534-Gene Expression, pubmed-meshheading:9506534-Golgi Apparatus, pubmed-meshheading:9506534-Humans, pubmed-meshheading:9506534-Melanoma, pubmed-meshheading:9506534-Microscopy, Confocal, pubmed-meshheading:9506534-Multidrug Resistance-Associated Proteins, pubmed-meshheading:9506534-P-Glycoprotein, pubmed-meshheading:9506534-Probenecid, pubmed-meshheading:9506534-RNA, Messenger, pubmed-meshheading:9506534-RNA, Neoplasm, pubmed-meshheading:9506534-Tumor Cells, Cultured
pubmed:year
1998
pubmed:articleTitle
Detection of P-glycoprotein in the Golgi apparatus of drug-untreated human melanoma cells.
pubmed:affiliation
Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't