Home LiteratureArticle Details
PMID: 1385112 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression.

The EMBO journal ·Vol. 11 ·No. 12 ·1992-12-00 ·Pages 4291-303

Trezise AE, Romano PR, Gill DR, Hyde SC, Sepúlveda FV, Buchwald M, Higgins CF

Abstract

The cystic fibrosis gene product, CFTR, and the multidrug resistance P-glycoprotein (encoded by the MDR1 gene) are structurally related proteins and both are associated with epithelial chloride channel activities. We have compared their cell-specific expression in the rat by in situ hybridization. In all tissues examined the two genes were found to have complementary patterns of expression, demonstrating exquisite regulation in both cell-specific and temporal fashions. Additionally, a switch in expression from one gene to the other was observed in certain tissues. For example, expression in the intestine switches from CFTR to MDR1 as the cells migrate across the crypt-villus boundary. A switch from CFTR to MDR1 expression was also observed in the uterine epithelium upon pregnancy. These data suggest that CFTR and P-glycoprotein serve analogous roles in epithelial cells and provide additional evidence that P-glycoprotein has a physiological role in regulating epithelial cell volume. The patterns of expression suggest that the regulation of these two genes is coordinately controlled.

Related Genes
MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1 Animals Base Sequence Chloride Channels Cystic Fibrosis/genetics Cystic Fibrosis Transmembrane Conductance Regulator Drug Resistance/genetics Embryonic and Fetal Development/genetics Epithelium/metabolism Female Gene Expression Regulation In Situ Hybridization Intestinal Mucosa/metabolism Male Membrane Glycoproteins/genetics Membrane Proteins/genetics,metabolism Molecular Sequence Data Placenta/metabolism Pregnancy RNA Probes Rats Rats, Wistar Testis/metabolism Uterus/metabolism
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 Chloride Channels Membrane Glycoproteins Membrane Proteins RNA Probes Cystic Fibrosis Transmembrane Conductance Regulator
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Trezise A E
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Romano P R
Gill D R
Hyde S C
Sepúlveda F V
Buchwald M
Higgins C F
References (50)
50 references, click to expand
  1. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites.
    Proc Natl Acad Sci U S A. 1989 Jan;86(2):695-8 PMID: 2563168
  2. Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel.
    Cell. 1991 Sep 6;66(5):1027-36 PMID: 1716180
  3. The tissue dependent expression of hamster P-glycoprotein genes.
    FEBS Lett. 1988 Mar 14;229(2):329-32 PMID: 2894327
  4. Sequence of mdr3 cDNA encoding a human P-glycoprotein.
    Gene. 1988 Nov 30;71(2):401-11 PMID: 2906314
  5. The gene encoding multidrug resistance is induced and expressed at high levels during pregnancy in the secretory epithelium of the uterus.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4350-4 PMID: 3380797
  6. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins.
    Cell. 1986 Nov 7;47(3):371-80 PMID: 3768958
  7. Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein.
    Nature. 1992 Feb 27;355(6363):830-3 PMID: 1371598
  8. Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.
    EMBO J. 1992 Jul;11(7):2487-94 PMID: 1378393
  9. Separation of drug transport and chloride channel functions of the human multidrug resistance P-glycoprotein.
    Cell. 1992 Oct 2;71(1):23-32 PMID: 1382860
  10. P-glycoprotein content and mediation of vincristine efflux: correlation with the level of differentiation in luminal epithelium of mouse small intestine.
    Cancer Commun. 1991 May;3(5):159-65 PMID: 1675112
  11. Complete cDNA sequences encoding the Chinese hamster P-glycoprotein gene family.
    DNA Seq. 1991;2(2):89-101 PMID: 1685679
  12. Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies.
    Proc Natl Acad Sci U S A. 1990 Jan;87(1):152-6 PMID: 1688652
  13. Sex-dependent and independent expression of the P-glycoprotein isoforms in Chinese hamster.
    J Cell Physiol. 1990 Dec;145(3):398-408 PMID: 1703163
  14. Separate K+ and Cl- transport pathways are activated for regulatory volume decrease in jejunal villus cells.
    Am J Physiol. 1991 Mar;260(3 Pt 1):G405-15 PMID: 1706147
  15. The cystic fibrosis gene has a "housekeeping"-type promoter and is expressed at low levels in cells of epithelial origin.
    J Biol Chem. 1991 May 15;266(14):9140-4 PMID: 1709163
  16. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells.
    Cell. 1991 Jul 12;66(1):85-94 PMID: 1712673
  17. Characterization of the promoter region of the cystic fibrosis transmembrane conductance regulator gene.
    J Biol Chem. 1991 Dec 25;266(36):24471-6 PMID: 1722205
  18. Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus.
    Mol Reprod Dev. 1990 Feb;25(2):101-9 PMID: 1968749
  19. Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport.
    Nature. 1990 Jul 26;346(6282):362-5 PMID: 1973824
  20. Colonic transepithelial potential difference in infants with cystic fibrosis.
    J Pediatr. 1991 Mar;118(3):412-5 PMID: 1999782
  21. New insights into the pathogenesis of cystic fibrosis.
    Scand J Gastroenterol Suppl. 1990;178:17-25 PMID: 2277966
  22. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein.
    J Histochem Cytochem. 1989 Feb;37(2):159-64 PMID: 2463300
  23. Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes.
    J Biol Chem. 1989 Jul 15;264(20):12053-62 PMID: 2473069
  24. Localization of the cystic fibrosis transmembrane conductance regulator in pancreas.
    J Clin Invest. 1991 Aug;88(2):712-6 PMID: 1713921
  25. In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator.
    Nature. 1991 Oct 3;353(6343):434-7 PMID: 1716739
  26. Immunocytochemical localization of the cystic fibrosis gene product CFTR.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9262-6 PMID: 1718002
  27. Regulatory volume decrease in small intestinal crypts is inhibited by K+ and Cl- channel blockers.
    Biochim Biophys Acta. 1991 Dec 9;1070(2):501-4 PMID: 1722422
  28. Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities.
    Mol Cell Biol. 1990 Apr;10(4):1652-63 PMID: 1969610
  29. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues.
    J Histochem Cytochem. 1990 Sep;38(9):1277-87 PMID: 1974900
  30. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):7160-4 PMID: 1976252
  31. Cystic fibrosis: a disease in electrolyte transport.
    FASEB J. 1990 Jul;4(10):2709-17 PMID: 2197151
  32. Expression of a multidrug-resistance gene in human tumors and tissues.
    Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9 PMID: 2432605
  33. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735-8 PMID: 2444983
  34. Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells.
    J Membr Biol. 1988 Oct;105(2):131-42 PMID: 2464063
  35. Membrane mechanisms in volume and pH regulation in vertebrate cells.
    Physiol Rev. 1989 Apr;69(2):315-82 PMID: 2538851
  36. Mammalian multidrug-resistance gene: correlation of exon organization with structural domains and duplication of an ancestral gene.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6488-92 PMID: 2570420
  37. The biochemistry of P-glycoprotein-mediated multidrug resistance.
    Annu Rev Biochem. 1989;58:137-71 PMID: 2570548
  38. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells.
    Cell. 1986 Nov 7;47(3):381-9 PMID: 2876781
  39. Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16.
    Cancer Res. 1988 Apr 1;48(7):1926-9 PMID: 2894894
  40. Resistance to multiple chemotherapeutic agents in human cancer cells.
    Trends Pharmacol Sci. 1988 Feb;9(2):54-8 PMID: 3072730
  41. The functions of uterine secretions.
    J Reprod Fertil. 1988 Mar;82(2):875-92 PMID: 3283351
  42. Cloning and characterization of a second member of the mouse mdr gene family.
    Mol Cell Biol. 1988 Jul;8(7):2770-8 PMID: 3405218
  43. Definition of the stages of the cycle of the seminiferous epithelium in the rat.
    Ann N Y Acad Sci. 1952 Nov 20;55(4):548-73 PMID: 13139144
  44. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR).
    Cell. 1992 Feb 21;68(4):809-18 PMID: 1371239
  45. Swelling-induced and depolarization-induced C1-channels in normal and cystic fibrosis epithelial cells.
    Am J Physiol. 1991 Oct;261(4 Pt 1):C658-74 PMID: 1656769
  46. Cloning and characterization of a member of the rat multidrug resistance (mdr) gene family.
    Gene. 1991 Oct 15;106(2):229-36 PMID: 1682220
  47. Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase.
    Nature. 1991 Feb 28;349(6312):793-6 PMID: 1705665
  48. K+ and Cl- currents in enterocytes isolated from guinea-pig small intestinal villi.
    J Physiol. 1991 Mar;434:351-67 PMID: 1708821
  49. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity.
    Science. 1991 Jul 12;253(5016):202-5 PMID: 1712984
  50. Cation and anion transport pathways in volume regulatory response of human lymphocytes to hyposmotic media.
    Am J Physiol. 1985 May;248(5 Pt 1):C480-7 PMID: 2581453
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-12-00
Pages
4291-303
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557002
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com