Tissue distribution and induction of human multidrug resistant protein 3

George L. Scheffer, Marcel Kool, Marcel de Haas, J. Marleen L. de Vree, Adriana C.L.M. Pijnenborg, Diederik K. Bosman, Ronald P.J. Oude Elferink, Paul Van Der Valk, Piet Borst, Rik J. Scheper

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

238 Citaten (Scopus)

Samenvatting

The multidrug resistance protein (MRP) family consists of several members and, for some of these transporter proteins, distinct roles in multidrug resistance and normal tissue functions have been well established (MRP1 and MRP2) or are still under investigation (MRP3). MRP3 expression studies in human tissues have been largely restricted to the mRNA level. In this report we extended these studies and further explored MRP3 expression at the protein level. Western blot and immunohistochemistry with two MRP3-specific monoclonal antibodies, M311-9 and M311-21, showed MRP3 protein to be present in adrenal gland, and kidney and in tissues of the intestinal tract: colon, pancreas, gallbladder, and liver. In epithelia, MRP3 was found to be located at the basolateral sides of cell membranes. In normal liver, MRP3 was detected at lower levels than anticipated from the mRNA data and was found present mainly in the bile ducts. In livers from patients with various forms of cholestasis, MRP3 levels were frequently increased in the proliferative cholangiocytes, with sometimes additional staining of the basolateral membranes of the hepatocytes. This was especially evident in patients with type 3 progressive familial intrahepatic cholestasis. The present results support the view that MRP3 plays a role in the cholehepatic and enterohepatic circulation of bile and in protection within the biliary tree and tissues along the bile circulation route against toxic bile constituents. The possible functional roles for MRP3 in the adrenal gland and in the kidney remain as yet unknown. In a panel of 34 tumor samples of various histogenetic origins, distinct amounts of MRP3 were detected in a limited number of cases, including lung, ovarian, and pancreatic cancers. These findings may be of potential clinical relevance when considering the drug treatment regimens for these tumor types.

Originele taal-2Engels
Pagina's (van-tot)193-201
Aantal pagina's9
TijdschriftLaboratory Investigation
Volume82
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - feb. 2002
Extern gepubliceerdJa

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