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The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology.

Abstract：

:The human multidrug resistance ABC transporters provide a protective function in our body against a large number of toxic compounds. These proteins, residing in the plasma membrane, perform an active, ATP-dependent extrusion of such xenobiotics. However, the same proteins are also used by the tumor cells to fight various anticancer agents. ABCG2 is an important member of the multidrug resistance proteins, an 'ABC half transporter', which functions as a homodimer in the cell membrane. In this review, we provide a basic overview of ABCG2 function in physiology and drug metabolism, but concentrate on the discussion of mutations and polymorphisms discovered in this protein. Interestingly, a single nucleotide mutation, changing amino acid 482 from arginine to threonine or glycine in ABCG2, results in a major increase in the catalytic activity and a wider drug recognition by this protein. Still, this mutation proved to be an in vitro artifact, produced only in heavily drug-selected cell lines. In contrast, at least two, but possibly more polymorphic variants of ABCG2 were found to be present in large human populations with different ethnic background. However, currently available experimental data regarding the cellular expression, localization and function of these ABCG2 variants are strongly contradictory. Since, the proteins produced by these variant alleles may differently modulate cancer treatment, general drug absorption and toxicity, may represent risk factors in fetal toxicity, or alter the differentiation of stem cells, their exact characterization is a major challenge in this field.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Cervenak J,Andrikovics H,Ozvegy-Laczka C,Tordai A,Német K,Váradi A,Sarkadi B

doi

10.1016/j.canlet.2005.01.061

keywords:

subject

Has Abstract

pub_date

2006-03-08 00:00:00

pages

62-72

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(05)00926-2

journal_volume

234

pub_type

杂志文章,评审

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