How to make P-glycoprotein (ABCB1, MDR1) harbor mutations and measure its expression and activity in cell cultures?

Several polymorphisms have been identified in ABCB1, the gene encoding for the P-glycoprotein. This transporter alters the pharmacokinetics or effectiveness of drugs by excreting them from cells where it is expressed (e.g., blood-brain barrier, intestine or tumors). No consensus has been reached reg...

Full description

Saved in:
Bibliographic Details
Published in:Pharmacogenomics 2018-11, Vol.19 (16), p.1285-1297
Main Authors: Zubiaur, Pablo, Saiz-Rodríguez, Miriam, Koller, Dora, Ovejero-Benito, María Carmen, Wojnicz, Aneta, Abad-Santos, Francisco
Format: Article
Language:English
Subjects:
Adenoviruses
ATP Binding Cassette Transporter, Subfamily B - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
Bioavailability
Biochemistry
Biological Transport - genetics
Biopsy
Blood-brain barrier
Brain tumors
Cancer
Cell culture
Cell Line
Chemotherapy
Cytokines
Deoxyribonucleic acid
DNA
Drug resistance
Genomes
Genotype & phenotype
Glycoproteins
Humans
Intestine
MDR1 protein
Mutagenesis
Mutation
Mutation - genetics
P-Glycoprotein
Pharmacokinetics
Plasmids
Polymorphism, Single Nucleotide - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Several polymorphisms have been identified in ABCB1, the gene encoding for the P-glycoprotein. This transporter alters the pharmacokinetics or effectiveness of drugs by excreting them from cells where it is expressed (e.g., blood-brain barrier, intestine or tumors). No consensus has been reached regarding the functional consequences of these polymorphisms in the transporter's function. The aim of this review was to describe a methodology that allows the assessment of P-gp function when harboring polymorphisms. We describe how to obtain cell lines with high expression levels of the transporter with polymorphisms and several tactics to measure its expression and activity. This methodology may help elucidate the contribution of polymorphisms in ABCB1 to drug pharmacokinetics, effectiveness and safety or to cancer chemotherapy failure.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2018-0101