Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo

Proceedings of the National Academy of Sciences of the United States of America
Sheng ZhouBrian P Sorrentino

Abstract

Hematopoietic stem cells (HSCs) can be identified by a "side population" (SP) phenotype. Previous studies have implicated the ATP binding cassette transporter genes Mdr1a/1b and/or Bcrp1 in the SP phenotype. To define the relative role of these transporters, we generated Bcrp1 null mice and evaluated HSCs both functionally and phenotypically. Loss of Bcrp1 gene expression, but not Mdr1a/1b, led to a significant reduction in the number of SP cells in the bone marrow and in skeletal muscle. In the bone marrow, there was a nearly absolute loss of lineage negative, c-Kit-positive, Sca-1-positive SP cells, and the residual SP cells were depleted of repopulating cells in a transplant assay, demonstrating that Bcrp1 expression is necessary for the SP phenotype in HSCs. Furthermore, Bcrp1 null hematopoietic cells were significantly more sensitive to mitoxantrone in drug-treated transplanted mice. These results show that Bcrp1 gene expression alone defines the SP stem cell phenotype, and suggest that the physiological function of Bcrp1 expression in HSCs is to provide protection from cytotoxic substrates.

References

Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·G J Spangrude, G R Johnson
Jan 26, 1996·The Journal of Biological Chemistry·M MüllerB Sarkadi
Apr 1, 1996·The Journal of Experimental Medicine·M A GoodellR C Mulligan
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·A H SchinkelP Borst
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·K A JacksonM A Goodell
Jul 6, 2000·Cytometry·R Hulspas, P J Quesenberry
Oct 19, 2000·Journal of the National Cancer Institute·J W JonkerA H Schinkel

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Citations

Apr 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wei-Wei ShenGuo-Hui Fu
Sep 15, 2005·Die Naturwissenschaften·Toshihisa IshikawaHiroshi Nakagawa
Sep 20, 2006·Pflügers Archiv : European journal of physiology·Hiroyuki Kusuhara, Yuichi Sugiyama
Sep 15, 2005·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Partha Krishnamurthy, John D Schuetz
Feb 27, 2007·Cancer Metastasis Reviews·Robert W RobeySusan E Bates
Sep 28, 2005·Digestive Diseases and Sciences·Sunny Zaheed HussainJohn F Tisdale
Oct 21, 2011·Journal of Molecular Histology·A KoniecznaJ Ehrmann
May 12, 2005·Journal of Mammary Gland Biology and Neoplasia·Matthew J Smalley, Robert B Clarke
Feb 19, 2009·Journal of Mammary Gland Biology and Neoplasia·Michael Dean
Aug 3, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Baoshan CaoJun Ren
Oct 7, 2009·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Kazuharu KaiHideyuki Saya
Mar 26, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jun Dou, Ning Gu
Jan 22, 2004·Archives of Medical Research·Albertus W WognumTerry E Thomas
Apr 27, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiao-qin ZhaoLi-Wu Fu
Apr 7, 2005·Neuroscience Research·Mohammed Omedul IslamJun Miyake
Jun 9, 2005·Progress in Retinal and Eye Research·Ani V DasIqbal Ahmad
Aug 7, 2003·Experimental Hematology·Gary Van Zant, Ying Liang
Apr 15, 2003·Trends in Cardiovascular Medicine·Atsushi Asakura
Jul 21, 2011·Molecular Pharmaceutics·Chung-Pu WuYu-Shan Wu
Apr 2, 2005·Nature Reviews. Cancer·Michael DeanSusan Bates
Jan 16, 2010·Nature Reviews. Cancer·Jamie I FletcherMurray D Norris
Jul 19, 2006·Stem Cells and Development·Soo Kyung KangSeung Heun Cha
Nov 15, 2007·Stem Cells and Development·Mi-Kyung Kang, Soo-Kyung Kang
Apr 9, 2009·Pathology International·Noriyuki SatoToshihiko Torigoe
Jan 28, 2010·Pharmacological Reviews·Curtis D Klaassen, Lauren M Aleksunes
Jul 9, 2008·Biochemistry. Biokhimii︠a︡·A A Stavrovskaya, T P Stromskaya
Nov 25, 2003·Gut·C G DietrichR P J Oude Elferink
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·P Krishnamurthy, J D Schuetz
Feb 24, 2004·Annual Review of Physiology·Mark A Sussman, Piero Anversa
Dec 13, 2006·American Journal of Respiratory and Critical Care Medicine·Adam GiangrecoSam M Janes

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