Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82121
Title:
Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer.
Authors:
Atkinson, Diane E; Greenwood, Susan L; Sibley, Colin P; Glazier, Jocelyn D; Fairbairn, Leslie J
Abstract:
Natural differences in expression and retroviral transduction techniques were used to test the hypothesis that MDR1 P-glycoprotein (P-gp) and MRP1 (multidrug resistance-related protein) contribute to xenobiotic handling by placental trophoblast. RT-PCR and Western blotting in placenta, primary cytotrophoblast cell cultures, and BeWo, JAr, and JEG choriocarcinoma cell lines showed that MRP1 was ubiquitously expressed, whereas MDR1 was absent or minimally expressed in BeWo and JEG cell lines. In syncytiotrophoblast, P-gp was localized predominantly to the microvillous, maternal facing plasma membrane, and MRP1 to the basal, fetal facing plasma membrane. Functional studies showed that cyclosporin A-sensitive accumulation of [3H]vinblastine by cells containing both transport proteins was significantly different from those expressing predominantly MRP1. Retroviral gene transfer of MDR1 to BeWo cells confirmed that this difference was due to the relative expression of MDR1. Therefore, both P-gp and MRP1 contribute to xenobiotic handling by the trophoblast. Localization of P-gp to the microvillous membrane suggests an essential role in preventing xenobiotic accumulation by the syncytiotrophoblast and, therefore, in protecting the fetus.
Affiliation:
Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Hathersage Rd., Manchester M13 OJH, United Kingdom. diane.e.atkinson@man.ac.uk
Citation:
Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. 2003, 285 (3):C584-91 Am. J. Physiol., Cell Physiol.
Journal:
American Journal of Physiology. Cell Physiology
Issue Date:
Sep-2003
URI:
http://hdl.handle.net/10541/82121
DOI:
10.1152/ajpcell.00418.2002
PubMed ID:
12724138
Type:
Article
Language:
en
ISSN:
0363-6143
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAtkinson, Diane E-
dc.contributor.authorGreenwood, Susan L-
dc.contributor.authorSibley, Colin P-
dc.contributor.authorGlazier, Jocelyn D-
dc.contributor.authorFairbairn, Leslie J-
dc.date.accessioned2009-09-22T14:48:00Z-
dc.date.available2009-09-22T14:48:00Z-
dc.date.issued2003-09-
dc.identifier.citationRole of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. 2003, 285 (3):C584-91 Am. J. Physiol., Cell Physiol.en
dc.identifier.issn0363-6143-
dc.identifier.pmid12724138-
dc.identifier.doi10.1152/ajpcell.00418.2002-
dc.identifier.urihttp://hdl.handle.net/10541/82121-
dc.description.abstractNatural differences in expression and retroviral transduction techniques were used to test the hypothesis that MDR1 P-glycoprotein (P-gp) and MRP1 (multidrug resistance-related protein) contribute to xenobiotic handling by placental trophoblast. RT-PCR and Western blotting in placenta, primary cytotrophoblast cell cultures, and BeWo, JAr, and JEG choriocarcinoma cell lines showed that MRP1 was ubiquitously expressed, whereas MDR1 was absent or minimally expressed in BeWo and JEG cell lines. In syncytiotrophoblast, P-gp was localized predominantly to the microvillous, maternal facing plasma membrane, and MRP1 to the basal, fetal facing plasma membrane. Functional studies showed that cyclosporin A-sensitive accumulation of [3H]vinblastine by cells containing both transport proteins was significantly different from those expressing predominantly MRP1. Retroviral gene transfer of MDR1 to BeWo cells confirmed that this difference was due to the relative expression of MDR1. Therefore, both P-gp and MRP1 contribute to xenobiotic handling by the trophoblast. Localization of P-gp to the microvillous membrane suggests an essential role in preventing xenobiotic accumulation by the syncytiotrophoblast and, therefore, in protecting the fetus.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subjectUterine Canceren
dc.subject.meshBlotting, Western-
dc.subject.meshChoriocarcinoma-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshGene Transfer Techniques-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMultidrug Resistance-Associated Proteins-
dc.subject.meshP-Glycoprotein-
dc.subject.meshPregnancy-
dc.subject.meshRNA, Messenger-
dc.subject.meshRetroviridae-
dc.subject.meshTransduction, Genetic-
dc.subject.meshTrophoblasts-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUterine Neoplasms-
dc.titleRole of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer.en
dc.typeArticleen
dc.contributor.departmentAcademic Unit of Child Health, University of Manchester, St Mary's Hospital, Hathersage Rd., Manchester M13 OJH, United Kingdom. diane.e.atkinson@man.ac.uken
dc.identifier.journalAmerican Journal of Physiology. Cell Physiologyen

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