title: Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology.
abstract: OBJECTIVE
  To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development.
  
  
  METHODS
  Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohn's disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1/Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function.
  
  
  RESULTS
  Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of host-microbiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak.
  
  
  CONCLUSIONS
  ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Svenningsen
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Lina Almind
authors.initials: LA
authors.lastname: Knudsen
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Stensballe
authors.affiliation: Vibeke Andersen, Katrine Svenningsen, Lina Almind Knudsen, Molecular Diagnostic and Clinical Health Research Unit, Hospital of Southern Jutland, 6200 Aabenraa, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008822:Mice, Transgenic; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D059016:Tumor Microenvironment
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human
keywords: ATP-binding cassette transporters; Adenoma-carcinoma sequence; Colorectal cancer; Inflammation; Inflammatory bowel disease; Intestinal