Cellular Localization of the Multidrug-Resistance Gene Product P-glycoprotein in Normal Human Tissues

Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated in a small number of specific sites. Most tissues examined revealed very little P-glycoprotein. Howev...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1987-11, Vol.84 (21), p.7735-7738
Main Authors: Thiebaut, Franz, Tsuruo, Takashi, Hamada, Hirofumi, Gottesman, Michael M., Pastan, Ira, Willingham, Mark C.
Format: Article
Language:English
Subjects:
3T3 cells
Analytical, structural and metabolic biochemistry
Antibodies, Monoclonal
Antineoplastics
ATP Binding Cassette Transporter, Subfamily B, Member 1
Biological and medical sciences
Cell lines
Drug Resistance
Epithelial cells
Epitopes - analysis
Fundamental and applied biological sciences. Psychology
Genes
Glycoproteins
Hepatocytes
Humans
Immunoenzyme Techniques
Immunohistochemistry
Jejunum
KB cells
Kidneys
Liver
Membrane Glycoproteins - analysis
Membrane Glycoproteins - genetics
Organ Specificity
Proteins
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Summary:Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated in a small number of specific sites. Most tissues examined revealed very little P-glycoprotein. However, certain cell types in liver, pancreas, kidney, colon, and jejunum showed specific localization of P-glycoprotein. In liver, P-glycoprotein was found exclusively on the biliary canalicular front of hepatocytes and on the apical surface of epithelial cells in small biliary ductules. In pancreas, P-glycoprotein was found on the apical surface of the epithelial cells of small ductules but not larger pancreatic ducts. In kidney, P-glycoprotein was found concentrated on the apical surface of epithelial cells of the proximal tubules. Colon and jejunum both showed high levels of P-glycoprotein on the apical surfaces of superficial columnar epithelial cells. Adrenal gland showed high levels of P-glycoprotein diffusely distributed on the surface of cells in both the cortex and medulla. These results suggest that the protein has a role in the normal secretion of metabolites and certain anti-cancer drugs into bile, urine, and directly into the lumen of the gastrointestinal tract.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.21.7735