RNAi Analysis of the ATP-binding Cassette (ABC) Family of Proteins

大量的相关基因表达数据显示，ABC蛋白家族关键成员的表达与对许多最常用抗癌化疗药物的耐药性之间存在联系。目前分析多重耐药（MDR）蛋白表达的直接功能后果的方法受到药物抑制剂缺乏特异性以及肿瘤细胞发生MDR时这些蛋白可能重叠的功能影响的阻碍。CCR细胞生物学实验室最近发现了一种化合物，它似乎对过度表达MDR-1 （ABCB1）的细胞具有特异性的细胞毒性。使用完全表征的与ABCB1对应的sirna，我们现在已经证明MDR-1的表达确实调节了细胞对这种化合物的敏感性。这项工作现已发表。我们还参与了一项由。Calcagno和Ambudkar （LCB， CCR， NCI）研究了ABCG2在耐药中的作用。描述这项工作的手稿已经提交。

Extensive associative gene expression data has been developed showing links between the expression of key members of the ABC family of proteins and resistance to many of the most commonly used anti-cancer chemotherapeutic agents. Current methods to analyze the direct functional consequence of the expression of the multiple drug resistance (MDR) proteins has been hampered by the lack of specificity of drug inhibitors, and the probable overlapping functional effect of these proteins when tumor cells develop MDR. The Laboratory of Cell Biology, CCR has recently identified a compound that appears to specifically be cytotoxic to cells over expressing MDR-1 (ABCB1). Using fully characterized siRNAs corresponding to ABCB1 we have now shown that MDR-1 expression does modulate the sensitivity of cells to this compound. This work has now been published. We have also been involved in a study conducted by Drs. Calcagno and Ambudkar (LCB, CCR, NCI) investigating the role of ABCG2 in drug resistance. A manuscript describing this work has been submitted.