Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis.
OBJECTIVE
The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis.


METHODS
Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry.


RESULTS
We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%.


CONCLUSIONS
BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies.
Zimmermann
Christian
C
Department of Clinical Pharmacology, University Hospital of Basel, Basel, Switzerland.
Hruz
Petr
P
Gutmann
Heike
H
Terracciano
Luigi
L
Beuers
Ulrich
U
Lehmann
Frank
F
Beglinger
Christoph
C
Drewe
Juergen
J
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000367:Age Factors; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000503:physiopathology; D015992:Body Mass Index; D002779:Cholestasis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D004386:Duodenum / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D009363:Neoplasm Proteins; D012333:RNA, Messenger