Download Gene Section ABCC1 (ATP-binding cassette, sub-family C

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in Oncology and Haematology
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Gene Section
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ABCC1 (ATP-binding cassette, sub-family C
(CFTR/MRP), member 1)
Franck Viguié
Laboratoire de Cytogénétique - Service d'Hématologie Biologique, Hôpital Hôtel-Dieu, 75181 Paris
Cedex 04, France (FV)
Published in Atlas Database: November 1998
Online updated version : http://AtlasGeneticsOncology.org/Genes/MRPID106.html
DOI: 10.4267/2042/37476
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 1999 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Localisation
Identity
Other names: MRP
associated protein)
HGNC (Hugo): ABCC1
Location: 16p13.1
Note: MRP is a gene
resistance, discovered in
glycoprotein negative,
carcinoma cell line.
(multidrug
In normal cells, predominant localisation in the
cytoplasm; in tumor cells, predominant in plasma
membrane, but also found in endoplasmic
reticulum, indicating a probable different function
as in normal cells.
resistance-
Function
involved in multidrug
a multidrug-resistant, Pnon small cell lung
Plasma membrane drug-efflux pump; MRP induces
a multidrug resistance phenotype (MDR
phenotype); overexpression confers tumor cell
resistance to a wide variety of hydrophobic drugs:
doxorubicin, daunorubicin, vinblastine, vincristine,
colchicine, VP16, Rhodamin 123; glutathione is
required for the effective expulsion of the
chemotherapeutic agents; the mode of action of
MRP is very similar to the one of P-glycoprotein,
the main protein responsible for the MDR
phenotype; however, MRP does not confer
resistance to Taxol or m-AMSA, but it is able to
transport metallic oxyanions, glutathione and other
glutathione conjugates; inhibitors of organic anion
transport, such as probenecid, can block MRP
activity.
DNA/RNA
Description
Spans at least 200 kb and contains 31 exons
Transcription
7 kb mRNA transcript; significant level of variant
transcripts due to alternative splicing.
Protein
Description
1531 amino acids, 190 kDa; contains two ATP
binding domains and three membrane-spanning
helices; member of the ATP-binding cassette
proteins (ABC proteins).
Homology
Structural and/or functional homology with other
ABC transporter proteins (CFTR, Pgp, MOAT).
Expression
Implicated in
Expressed at a basal level in a wide variety of
normal tissues, including epithelial cells and all
hematopoietic cell types, which suggests a function
common to most cell types; increased expression in
various tumor cell type.
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(1)
Induced resistance to
chemotherapeutic agents
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ABCC1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 1)
multidrug resistance-associated protein (MRP) in acute
and chronic leukemias. Leukemia. 1994 Jun;8(6):990-7
Disease
In a wide variety of solid and hematological
tumors.
Oncogenesis
MRP hyperexpression may confer therapeutic
resistance in leukemia and solid tumor; however its
relative importance, in comparison with other
proteins able to induce the MDR phenotype (P-gp,
LRP), is not yet clear; hyperexpression is probably
linked to transcriptional activation of the gene
and/or increased mRNA stability, and not to gene
amplification; increased expression of MRP mRNA
and protein is a factor of bad prognostic in
neuroblastoma, retinoblastoma, and non small cell
lung carcinoma. In haematological malignancies,
overexpression is frequent in chronic lymphocytic
leukemia and prolymphocytic leukemia, occasional
in acute myeloid leukemia and rare in acute
lymphoid leukemia, lymphoma, multiple myeloma
and myeloproliferative disorders.
Zaman GJ, Flens MJ, van Leusden MR, de Haas M,
Mülder HS, Lankelma J, Pinedo HM, Scheper RJ, Baas F,
Broxterman HJ. The human multidrug resistanceassociated protein MRP is a plasma membrane drug-efflux
pump. Proc Natl Acad Sci U S A. 1994 Sep
13;91(19):8822-6
Barrand MA, Bagrij T, Neo SY. Multidrug resistanceassociated protein: a protein distinct from P-glycoprotein
involved in cytotoxic drug expulsion. Gen Pharmacol. 1997
May;28(5):639-45
Deeley RG, Cole SP. Function, evolution and structure of
multidrug resistance protein (MRP). Semin Cancer Biol.
1997 Jun;8(3):193-204
Kavallaris M. The role of multidrug resistance-associated
protein (MRP) expression in multidrug resistance.
Anticancer Drugs. 1997 Jan;8(1):17-25
Ling V. Multidrug resistance: molecular mechanisms and
clinical relevance. Cancer Chemother Pharmacol. 1997;40
Suppl:S3-8
Willman CL. 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. Semin
Hematol. 1997 Oct;34(4 Suppl 5):25-33
References
Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE,
Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley
RG. Overexpression of a transporter gene in a multidrugresistant human lung cancer cell line. Science. 1992 Dec
4;258(5088):1650-4
This article should be referenced as such:
Viguié F. ABCC1 (ATP-binding cassette, sub-family C
(CFTR/MRP), member 1). Atlas Genet Cytogenet Oncol
Haematol. 1999; 3(1):11-12.
Burger H, Nooter K, Zaman GJ, Sonneveld P, van
Wingerden KE, Oostrum RG, Stoter G. Expression of the
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(1)
Viguié F
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