title: Functional analysis of CFTR chloride channel activity in cells with elevated MDR1 expression.
abstract: Using the patch-clamp method, we investigated a relationship between MDR1 expression and its effects on the CFTR channel function. Incubation of CaCo-2 cells with increasing concentrations of doxorubicin resulted in a reduction of CFTR chloride channel activity in a dose-dependent manner. This reduction was associated with a decrease of CFTR mRNA and simultaneous up-regulation of MDR1 mRNA in the presence of doxorubicin. Similar alteration of the CFTR function was observed in CaCo-2 cells transiently overexpressing MDR1. No alterations of the cAMP-dependent chloride currents were observed in COS-1 cells transiently co-expressing CFTR and MDR1 from strong CMV promoters. This indicated that repression of CFTR by MDR1 induction requires the presence of the native CFTR promoter.
authors.affiliation: Laboratory of Physiology, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium. grzegorz.owsianik@med.kuleuven.ac.be
authors.forename: Lishuang
authors.initials: L
authors.lastname: Cao
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
authors.forename: Martine
authors.initials: M
authors.lastname: Jaspers
authors.forename: Annelies
authors.initials: A
authors.lastname: Janssens
authors.forename: Harry
authors.initials: H
authors.lastname: Cuppens
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D004553:Electric Conductivity; D015870:Gene Expression; D006801:Humans; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C505032:CFTR protein, human; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004317:Doxorubicin