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

广泛的关联基因表达数据已被开发，显示ABC家族蛋白质的关键成员的表达与对许多最常用的抗癌化疗剂的抗性之间的联系。目前分析多药耐药（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当肿瘤细胞发生MDR时这些蛋白可能重叠的功能作用的阻碍。CCR细胞生物学实验室最近发现了一种化合物，该化合物似乎对过表达MDR-1（ABCB 1）的细胞具有特异性细胞毒性。使用完全表征的对应于ABCB 1的siRNA，我们现在已经表明MDR-1表达确实调节细胞对该化合物的敏感性。这项工作现已出版。我们还参与了由Calcagno和Ambudkar博士（LCB，CCR，NCI）进行的一项研究，调查ABCG 2在耐药性中的作用。目前正在编写一份介绍这项工作的手稿。

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 is currently in preparation.