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First published online July 7, 2005
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Submitted on April 4, 2005
Accepted on June 21, 2005

Rapid Communication

Contribution of the ABC-transporters Bcrp1 and Mdr1a/1b to the side population phenotype in mammary gland

Johan W. Jonker 1, Jamie Freeman 2, Ellen Bolscher 1, Sandra Musters 1, Azra J. Alvi 3, Ian Titley 3, Alfred H. Schinkel 1*, Trevor C. Dale 2

1 The Netherlands Cancer Institute, Division of Experimental Therapy
2 School of Biosciences, Cardiff University, Cardiff CF10 3US, U.K.
3 Institute of Cancer Research, Section of Cell and Molecular Biology, London, U.K.

* To whom correspondence should be addressed. E-mail: a.schinkel{at}nki.nl.


  Abstract

The ability of cells to export Hoechst 33342 can be used to identify a subpopulation of cells (side population, SP) with characteristics of stem cells in many tissues. The ABC-transporters Bcrp1 (Abcg2) and Mdr1a/1b (Abcb1a/1b) have been implicated as being responsible for this phenotype. To further explore the involvement of these transporters in the SP phenotype we have generated Bcrp1/Mdr1a/1b triple knockout mice and studied the effect of their absence on the SP in bone marrow and mammary gland. Whereas in bone marrow Bcrp1 was almost exclusively responsible for the SP, in contrast, both transporters contributed to the SP phenotype in the mammary gland where their combined absence resulted in a nearly complete loss of SP. Interestingly, bone marrow of Mdr1a/1b-/- mice frequently displayed an elevated SP which was reversible by the Bcrp1 inhibitor Ko143, suggesting that Bcrp1 can compensate for the loss of Mdr1a/1b in bone marrow.




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