Abstract
The molecular genetic characterization of MDR human, mouse, and hamster P-glycoprotein genes has identified several elements that may contribute to the diversity in multidrug-resistance phenotype associated with P-glycoprotein expression. First, spontaneous mutations within the MDR genes may alter the relative affinity of P-glycoprotein for certain drugs or alter the substrate specificity of the protein. Secondly, alternative splicing of MDR mRNA may result in isoforms with different substrate recognition or transport properties. Differential splicing has not thus far been demonstrated for human MDR1 or mouse mdr1a and mdr1b genes. Finally, differential expression of mdr genes encoding P-glycoprotein isoforms with distinct properties appears to be a possible mechanism for generating diversity in MDR rodent cells.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Amino Acid Sequence
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Animals
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Biological Transport, Active
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics*
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Carrier Proteins / physiology
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Cricetinae / genetics
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Drug Resistance
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Gene Amplification
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Gene Expression Regulation
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Gene Expression Regulation, Neoplastic
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Genes
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Humans
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / physiology
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Mice / genetics
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Models, Molecular
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Molecular Sequence Data
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Multigene Family
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Organ Specificity
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Promoter Regions, Genetic
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Protein Processing, Post-Translational
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Species Specificity
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Substrate Specificity
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Transcription Factors / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Carrier Proteins
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Membrane Glycoproteins
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Neoplasm Proteins
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Transcription Factors