title: Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Zimmermann
authors.forename: Petr
authors.initials: P
authors.lastname: Hruz
authors.forename: Heike
authors.initials: H
authors.lastname: Gutmann
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Frank
authors.initials: F
authors.lastname: Lehmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.forename: Juergen
authors.initials: J
authors.lastname: Drewe
mesh_terms: 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
chemical_list: 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