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Breast Cancer Resistance Protein (BCRP/ABCG2) Is Expressed by Progenitor Cells/Reactive Ductules and Hepatocytes and Its Expression Pattern Is Influenced by Disease Etiology and Species Type: Possible Functional Consequences

Sara Vander Borght, Louis Libbrecht, Aezam Katoonizadeh, Jos van Pelt, David Cassiman, Frederik Nevens, Alfons Van Lommel, Bryon E. Petersen, Johan Fevery, Peter L. Jansen and Tania A. Roskams

Laboratory of Morphology and Molecular Pathology (SVB,LL,AVL,TAR), Laboratory of Hepatology (AK,JvP,DC,FN,JF), University Hospitals Leuven, Leuven, Belgium; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida (BEP); and Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands (PLJ)

Correspondence to: Sara Vander Borght, Minderbroederstraat 12, 3000 Leuven, Belgium. E-mail: Sara.vanderborght{at}uz.kuleuven.ac.be

Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette transport protein that is expressed in several organs including the liver. Previous studies have shown that ABC transport proteins play an important pathophysiological role in several liver diseases. However, to date, expression pattern and possible role of BCRP in human liver diseases and animal models have not been studied in detail. Here we investigated the expression pattern of BCRP in normal liver, chronic parenchymal and biliary human liver diseases, and parallel in different rat models of liver diseases. Expression was studied by immunohistochemistry and additionally by RT-PCR analysis in Thy-1-positive rat oval cells. Bile ducts, hepatic progenitor cells, reactive bile ductules, and blood vessel endothelium were immunoreactive for BCRP in normal liver and all types of human liver diseases and in rat models. BCRP was expressed by the canalicular membrane of hepatocytes in normal and diseased human liver, but never in rat liver. Remarkably, there was also expression of BCRP at the basolateral pole of human hepatocytes, and this was most pronounced in chronic biliary diseases. In conclusion, BCRP positivity in the progenitor cells/reactive ductules could contribute to the resistance of these cells to cytotoxic agents and xenotoxins. Basolateral hepatocytic expression in chronic biliary diseases may be an adaptive mechanism to pump bile constituents back into the sinusoidal blood. Strong differences between human and rat liver must be taken into account in future studies with animal models. (J Histochem Cytochem 54:1051–1059, 2006)

Key Words: breast cancer resistance protein • immunohistochemistry • basolateral expression • hepatic progenitor cells • multidrug resistance phenotype • human and rat liver

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