title: Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance.
abstract: OBJECTIVE
  To identify the exact length and possible length variations of the ABCB1 3'-UTR as important regulatory site for miRNA interaction of this drug transporter and its possible contribution to drug resistance.
  
  
  METHODS
  3'-RACE and various standard PCR experiments were performed using cDNA of different human cell lines and liver tissue. The abundance of 3'-UTR fragments was analyzed using quantitative RT-PCR.
  
  
  RESULTS
  Five different ABCB1 3'-UTR length variants were identified. miRNA binding sites were located only on the three longer fragments. Imatinib-resistant leukemia cells expressed predominantly shorter 3'-UTRs, where miRNA binding sites are absent.
  
  
  CONCLUSIONS
  Shortening of the ABCB1 3'-UTR causes loss of miRNA-dependent translational control leading to elevated ABCB1 protein levels.
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bruhn
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Drerup
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Kaehler
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Sierk
authors.initials: S
authors.lastname: Haenisch
authors.affiliation: Division of Molecular Oncology, Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Röder
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
mesh_terms: D020413:3' Untranslated Regions; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D019008:Drug Resistance, Neoplasm; D014644:Genetic Variation; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D035683:MicroRNAs; D000068877:Imatinib Mesylate
keywords: MDR1; P-glycoprotein; drug resistance; miRNA; polyadenylation; post-transcriptional regulation