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ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1

Written1998-03Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

Other aliasPGY1 (P glycoprotein1/ multidrug resistance 1)
MDR1 (multidrug resistance 1)
LocusID (NCBI) 5243
Atlas_Id 105
Location 7q21.12  [Link to chromosome band 7q21]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GRM3 (7q21.11) / ABCB1 (7q21.12)

DNA/RNA

Description spans on a 120 kb genomic fragment; separated from MDR3 gene (which is transcribed in the same direction) by only 34 kb of intergenic DNA
Transcription 5 kb mRNA

Protein

Description the protein is called P-glycoprotein; 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-term glycosylation; the N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide
Expression normally expressed at secretory surface of a number of tissues, including biliary canaliculi, proximal tubules of the kidney, intestinal and colonic epithelium; hematopoietic stem cells express high levels of P-glycoprotein; overexpressed in many multidrug resistant cell lines and in tumor cells resistant to chemotherapy
Localisation mainly at the cell membrane, with a secondary localisation at the Golgi apparatus
Function the P-glycoprotein is an energy-dependent efflux pump involved in extrusion of many types of lypophilic coumpounds; it may acts in normal tissues as a protective mechanism against noxious xenobiotics and as a transporter of endogenous substrates; in tumour cells, the drug efflux pump results in a decrease in intracellular drug concentration
Homology closely related gene to MDR3 (also called PGY3), located at the same chromosomal site but not implicated in multidrug resistance; there are 3 murine homolog genes (mdr1, mdr2, mdr3) out of which only 2 (mdr1 and mdr3) are involved in multidrug resistance; member of a large superfamily of transmembrane transporter proteins named ATP Binding Cassette (ABC) transporters or Traffic ATPases; structural homology with other ABC transporter proteins (CFTR, MRP)

Implicated in

Note
  
Entity tumor cells resistance
Disease tumor cells resistance to a wide variety of antineoplasic agents: doxorubicin, daunorubicin, vinblastine, vincristine, colchicine, actinomycine D, etoposide, tenoposide, mitoxantrone, homoharringtonine; this phenomenon is named "multidrug resistance" (MDR); P-glycoprotein is the main protein responsible for the MDR phenotype; however, other agents may be involved in MDR, independently or in association with P-glycoprotein: "multidrug resistant associated protein" (MRP), "lung resistance protein" (LRP), "anthracycline associated resistance protein" (ARX)
  
  
Entity leukemias
Disease In leukemia, MDR1 overexpression is observed in patients with a lower complete remission rate and with a shortening of overall survival; frequently associated with intermediate and poor prognosis karyotype; in AML, approximately 50% of patients are MDR positive at diagnosis (range 22-70%) and the MDR phenotype is more frequently observed in CD34+ leukemias; in ALL, the average number of MDR-positive cases is 22% at diagnosis
  
  
Entity tumour cell lines: in numerous continuous tumour cell lines which acquired experimentally a MDR phenotype when cultured with progressively increasing drug concentration, the acquisition of MDR was associated with hyperexpression of P-glycoprotein; for the higher levels of expression, southern blots revealed an increase in the number of copies of the MDR1 gene per cell
Cytogenetics the genomic amplification of MDR1 appears as extrachromosomic "double-minute chromosomes" (DM) or intrachromosomic "homogeneous staining regions" (HSR)
Oncogenesis amplification
  

Bibliography

Multidrug resistance in acute myeloid leukemia.
Baer MR, Bloomfield CD
Journal of the National Cancer Institute. 1991 ; 83 (10) : 663-665.
PMID 2023265
 
P-glycoprotein multidrug resistance and cancer.
Bosch I, Croop J
Biochimica et biophysica acta. 1996 ; 1288 (2) : F37-F54.
PMID 8876632
 
P-glycoprotein and multidrug resistance.
Gottesman MM, Pastan I, Ambudkar SV
Current opinion in genetics & development. 1996 ; 6 (5) : 610-617.
PMID 8939727
 
The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives.
Hegewisch-Becker S, Hossfeld DK
Annals of hematology. 1996 ; 72 (3) : 105-117.
PMID 8766251
 
Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment.
Hunault M, Zhou D, Delmer A, Ramond S, Viguié F, Cadiou M, Perrot JY, Levy V, Rio B, Cymbalista F, Zittoun R, Marie JP
Annals of hematology. 1997 ; 74 (2) : 65-71.
PMID 9063375
 
Functional expression of MDR-1 in acute myeloid leukemia: correlation with the clinical-biological, immunophenotypical, and prognostic disease characteristics.
Martínez A, San Miguel JF, Valverde B, Bárez A, Moro MJ, García-Marcos MA, Pérez-Simó JA, Vidriales B, Orfao A
Annals of hematology. 1997 ; 75 (3) : 81-86.
PMID 9368475
 
Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line.
Ruiz JC, Choi KH, von Hoff DD, Roninson IB, Wahl GM
Molecular and cellular biology. 1989 ; 9 (1) : 109-115.
PMID 2648129
 
Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells.
Schoenlein PV, Shen DW, Barrett JT, Pastan I, Gottesman MM
Molecular biology of the cell. 1992 ; 3 (5) : 507-520.
PMID 1611154
 
Cell biological mechanisms of multidrug resistance in tumors.
Simon SM, Schindler M
Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (9) : 3497-3504.
PMID 7909602
 
A YAC-based contig of 1.5 Mb spanning the human multidrug resistance gene region and delineating the amplification unit in three human multidrug-resistant cell lines.
Torigoe K, Sato S, Kusaba H, Kohno K, Kuwano M, Okumura K, Green ED, Tsui LC, Scherer SW, Schlessinger D, Wada M
Genome research. 1995 ; 5 (3) : 233-244.
PMID 8593611
 
The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program.
Willman CL
Seminars in hematology. 1997 ; 34 (4 Suppl 5) : 25-33.
PMID 9408958
 
Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonine-selected K562 human leukemia cell lines.
Zhou DC, Ramond S, Viguie F, Faussat AM, Zittoun R, Marie JP
International journal of cancer. Journal international du cancer. 1996 ; 65 (3) : 365-371.
PMID 8575859
 
MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia.
van den Heuvel-Eibrink MM, van der Holt B, te Boekhorst PA, Pieters R, Schoester M, Löwenberg B, Sonneveld P
British journal of haematology. 1997 ; 99 (1) : 76-83.
PMID 9359506
 

Citation

This paper should be referenced as such :
Viguié, F
ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1)
Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):45-46.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PGY1ID105.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  i(7)(q10)
idic(7)(q11.2)


External links

Nomenclature
Cards
AtlasPGY1ID105.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)5243
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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