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Breast cancer resistance protein and P-glycoprotein expression in patients with newly diagnosed and therapy-refractory ulcerative colitis compared with healthy controls

Gutmann, H. and Hruz, P. and Zimmermann, C. and Straumann, A. and Terracciano, L. and Hammann, F. and Lehmann, F. and Beglinger, C. and Drewe, J.. (2008) Breast cancer resistance protein and P-glycoprotein expression in patients with newly diagnosed and therapy-refractory ulcerative colitis compared with healthy controls. Digestion, 78 (2-3). pp. 154-162.

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Official URL: http://edoc.unibas.ch/dok/A6004889

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Abstract

AIMS: Efflux transporters such as breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (Pgp; MDR1/ABCB1) are protecting the enterocytes from potentially toxic compounds. Both transporters have been reported to be downregulated in patients with active ulcerative colitis (UC). The aim of this study was to evaluate transporter expression in both unaffected and inflamed mucosa of patients with active UC, in drug-naïve and treated patients with UC and compare the results with transporter expression in healthy subjects. METHODS: Transporter expression was determined with real-time RT-PCR (TaqMan) in inflamed and unaffected mucosa of newly diagnosed (n = 12) and therapy-refractory (n = 11) patients with UC. Expression levels were compared with UC patients in remission (n = 11) and control subjects (n = 26). BCRP and Pgp expression was evaluated by immunohistochemistry. RESULTS: Compared with unaffected mucosa, BCRP expression was significantly reduced in inflamed mucosa of newly diagnosed drug-naïve patients with UC (expression reduced to 30%) as well as in patients not responding to treatment (reduced to 25%) with either 5-aminosalicylates (n = 7) or prednisone (n = 4). Unaffected mucosa of UC patients showed comparable transporter expression to unaffected mucosa of control subjects. MDR1 expression depicts a similar pattern. Protein staining for Pgp and BCRP was significantly reduced in the inflamed mucosa of patients with active UC. CONCLUSIONS: Expression of both efflux transporters BCRP and MDR1 is reduced, but only in inflamed tissue of patients with active UC. Transporter expression in unaffected mucosa of patients with active UC is comparable to healthy controls. The data suggest that the inflammatory process is responsible for the reduced levels. A major role in the pathogenesis of UC is unlikely.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Gastroenterologie > Gastroenterologie (Beglinger)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Gastroenterologie > Gastroenterologie (Beglinger)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gastroenterology (Beglinger)
UniBasel Contributors:Terracciano, Luigi M. and Straumann, Alex and Gutmann, Heike and Drewe, Jürgen and Beglinger, Christoph and Lehmann, Frank Serge
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Karger
ISSN:0012-2823
e-ISSN:1421-9867
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:25 Oct 2017 08:12
Deposited On:07 Dec 2012 12:59

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