Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity.

A limited number of gene expression studies have investigated the quantitative relationships between the amount of transcript, level of protein or activity/function, with disparate conclusions regarding these relationships. Collectively these studies indicate that the relevance of quantitative transcript analysis as a predictor of phenotype has to be evaluated on a gene-by-gene or even a case-by-case basis. The purpose of this study was to define a suitable marker for MDR1-dependent drug efflux, and to quantitatively investigate the relationships between the amount of transcript, protein and drug efflux in the frequently used Caco-2 cell model.

Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population.

The ATP-binding cassette transporter ABCG2 (also named breast cancer resistance protein, BCRP) functions as a drug efflux transporter and is expressed at high levels in the human small intestine. The aim of this study was to screen the human ABCG2 gene for genetic variation. The regions of the gene most likely to affect function, namely the coding parts, exon/intron boundaries, 5' untranslated region and 3' untranslated region and the proposed promoter region, were included in the screening.