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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3881-3889. Prepublished online as a Blood First Edition Paper on August 17, 2006; DOI 10.1182/blood-2005-10-009084. This Article Full Text (PDF) All Versions of this Article: blood-2005-10-009084v1 108/12/3881    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Turner, J. G Articles by Sullivan, D. M. Search for Related Content PubMed PubMed Citation Articles by Turner, J. G Articles by Sullivan, D. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 12, 2005 Accepted July 24, 2006 ABCG2 expression, function and promoter methylation in human multiple myeloma Joel G Turner, Jana L. Gump, Chunchun Zhang, James M. Cook, Douglas Marchion, Lori Hazlehurst, Pamela Munster, Michael J. Schell, William S. Dalton, and Daniel M. Sullivan* H Lee Moffitt Cancer Center and Research Institute, USF, FL, USA University of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: sullivad{at}moffitt.usf.edu. We investigated the role of the breast cancer resistance protein (BCRP/ABCG2) in drug resistance in multiple myeloma (MM). Human MM cell lines, and MM patient plasma cells isolated from bone marrow, were evaluated for ABCG2 mRNA expression by quantitative PCR, and ABCG2 protein by Western blot analysis, immunofluorescence microscopy and flow cytometry. ABCG2 function was determined by measuring topotecan and doxorubicin efflux using flow cytometry, in the presence and absence of the specific ABCG2 inhibitor, tryprostatin A. The methylation of the ABCG2 promoter was determined using bisulfite sequencing. We found that ABCG2 expression in myeloma cell lines increased after exposure to topotecan and doxorubicin, and was greater in log-phase cells when compared to quiescent cells. Myeloma patients treated with topotecan had an increase in ABCG2 mRNA and protein expression after treatment with topotecan, and at relapse. Expression of ABCG2 is regulated, at least in part, by promoter methylation both in cell lines and in patient plasma cells. Demethylation of the promoter increased ABCG2 mRNA and protein expression. These findings suggest that ABCG2 is expressed and functional in human myeloma cells, regulated by promoter methylation, affected by cell density, upregulated in response to chemotherapy, and may contribute to intrinsic drug resistance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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