JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watts, G. S.
Right arrow Articles by Salmon, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watts, G. S.
Right arrow Articles by Salmon, S. E.

Vol. 299, Issue 2, 434-441, November 2001

cDNA Microarray Analysis of Multidrug Resistance: Doxorubicin Selection Produces Multiple Defects in Apoptosis Signaling Pathways

George S. Watts, Bernard W. Futscher, Robert Isett, Mary Gleason-Guzman, Mark W. Kunkel and Sydney E. Salmon

Arizona Cancer Center (G.S.W., M.G.G., R.I., S.E.S.) and Departments of Pharmacology (B.W.F.) and Pathology (M.W.K.), University of Arizona, Tucson, Arizona

Doxorubicin plays an important role in the treatment of leukemias, lymphomas, and a variety of carcinomas. Tumor cell resistance to doxorubicin is often associated with expression of the multidrug resistance gene MDR1, which codes for the drug efflux pump P-glycoprotein, and a multidrug-resistant phenotype. Evidence from multiple sources suggests, however, that additional genes besides MDR1 are involved in development of multidrug resistance. To identify genes involved in the multidrug resistance phenotype, we created a 5760-gene cDNA microarray to search for differentially expressed genes between the human multiple myeloma cell line RPMI 8226 and its doxorubicin-selected sublines 8226/Dox6 and 8226/Dox40, both of which express MDR1 and are multidrug-resistant. The cDNA microarray results identified a set of differentially expressed genes, which included MDR1 as expected. Thirty Northern analyses were used to confirm the results of the cDNA microarrays; comparison with the microarray results showed a 90% agreement between the two techniques. Within the set of differentially expressed genes identified by the cDNA microarrays, 29 were of particular interest as they can participate in apoptotic signaling, particularly as mediated by ceramide and the mitochondrial permeability transition. The functional importance of these changes in gene expression is supported by their explanation of the 8226/Dox cell lines' cross-resistance to substances that are not P-glycoprotein substrates, such as Fas/CD95 ligand and staurosporine. We conclude that doxorubicin selection led to changes in gene expression that reduce the apoptotic response to death-inducing stimuli and thus contribute to the multidrug resistance phenotype.

0022-3565/01/2992-0434$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 FASEB J.Home page
Y.-Y. Liu, J. Y. Yu, D. Yin, G. A. Patwardhan, V. Gupta, Y. Hirabayashi, W. M. Holleran, A. E. Giuliano, S. M. Jazwinski, V. Gouaze-Andersson, et al.
A role for ceramide in driving cancer cell resistance to doxorubicin
FASEB J, July 1, 2008; 22(7): 2541 - 2551.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J.-P. Gillet, T. Efferth, D. Steinbach, J. Hamels, F. de Longueville, V. Bertholet, and J. Remacle
Microarray-based Detection of Multidrug Resistance in Human Tumor Cells by Expression Profiling of ATP-binding Cassette Transporter Genes
Cancer Res., December 15, 2004; 64(24): 8987 - 8993.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Mahadevan and A. F. List
Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies
Blood, October 1, 2004; 104(7): 1940 - 1951.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. S. Sappal, A. K. McClendon, J. A. Fleming, V. Thoroddsen, K. Connolly, C. Reimer, R. K. Blackman, C. E. Bulawa, N. Osheroff, P. Charlton, et al.
Biological characterization of MLN944: A potent DNA binding agent
Mol. Cancer Ther., January 1, 2004; 3(1): 47 - 58.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
N. Babbar, N. A. Ignatenko, R. A. Casero Jr., and E. W. Gerner
Cyclooxygenase-independent Induction of Apoptosis by Sulindac Sulfone Is Mediated by Polyamines in Colon Cancer
J. Biol. Chem., November 28, 2003; 278(48): 47762 - 47775.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Aleman, J.-P. Annereau, X.-J. Liang, C. O. Cardarelli, B. Taylor, J. J. Yin, A. Aszalos, and M. M. Gottesman
P-Glycoprotein, Expressed in Multidrug Resistant Cells, Is Not Responsible for Alterations in Membrane Fluidity or Membrane Potential
Cancer Res., June 15, 2003; 63(12): 3084 - 3091.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. E. Lamendola, Z. Duan, R. Z. Yusuf, and M. V. Seiden
Molecular Description of Evolving Paclitaxel Resistance in the SKOV-3 Human Ovarian Carcinoma Cell Line
Cancer Res., May 1, 2003; 63(9): 2200 - 2205.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Burger, J. A. Foekens, M. P. Look, M. E. Meijer-van Gelder, J. G. M. Klijn, E. A. C. Wiemer, G. Stoter, and K. Nooter
RNA Expression of Breast Cancer Resistance Protein, Lung Resistance-related Protein, Multidrug Resistance-associated Proteins 1 and 2, and Multidrug Resistance Gene 1 in Breast Cancer: Correlation with Chemotherapeutic Response
Clin. Cancer Res., February 1, 2003; 9(2): 827 - 836.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.