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Received for publication January 6, 2005.
Revised May 12, 2005.
Accepted for publication May 17, 2005.
ATP-binding cassette (ABC) membrane proteins comprise a superfamily of transporters with a wide variety of substrates. Human has 49 members in this superfamily. Several human ABC transporters such as ABCB1 and ABCC1 have been attributed to cause multidrug resistance (MDR) in cancer treatment when over-expressed. Previously, a MDR cancer cell line MCF7/AdVp3000 has been selected and over-expression of ABCG2 was thought to cause MDR in this cell line. However, ectopic over-expression of ABCG2 in MCF7 cells could not explain the high drug resistance level observed with the selected cell line. In this study, we designed an AmpArray analysis to profile whether other ABC transporters were also selected to contribute to the increased drug resistance in MCF7/AdVp3000 cells. We found that 16 ABC transporters including ABCG2 had 
1.5-fold altered expression in MCF7/AdVp3000 compared with the parental MCF7 cells. Particularly, the expression of ABCA4 and ABCC3 was increased 132 and 459 fold, respectively, while ABCG2 was increased ~3000 fold. Furthermore, the elevated expression of these three transporters reversed with the reversed drug resistance phenotype and silencing ABCC3 expression in MCF7/AdVp3000 cells significantly reduced Adriamycin resistance. Thus, other ABC transporters in addition to ABCG2 likely contribute to the MDR selected in MCF7/AdVp3000 cells. This study also shows that AmpArray can be used as a quick and easy tool to profile the expression of ABC transporters in resistant cell lines and tumor samples for potential use in individualized design of therapy.
Key words:
MDR/p-Glycoprotein, Comparative genome analyses, Resistance
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