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

大量的关联基因表达数据已经显示出ABC蛋白家族关键成员的表达与许多最常用的抗癌化疗药物的耐药性之间的联系。目前分析多药耐药(MDR)蛋白表达的直接功能结果的方法受到药物抑制剂缺乏特异性以及这些蛋白在肿瘤细胞发生MDR时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似乎对过度表达MDR-1(ABCB1)的细胞具有特异性细胞毒性的化合物。使用完全表征的对应于ABCB1的siRNAs，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。这部作品现已出版。我们还参与了Calcagno博士和Ambukar博士(LCB、CCR、NCI)进行的一项研究，调查ABCG2在耐药性中的作用。目前正在准备一份描述这项工作的手稿。

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.