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

ATP 结合盒 (ABC) 蛋白质家族的 RNAi 分析

• 批准号: 7592797
• 负责人: natasha caplen
• 金额: $ 1.4万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592797
• 关键词: ABCB1 gene; ABCG2 gene; ATP-Binding Cassette Transporters; Binding; CCR; Cells; Cellular biology; Clinical; Data; Development; Drug resistance; Family; Gene Expression; Glycoproteins; Laboratories; Lead; Link; Malignant Neoplasms; Manuscripts; Methods; Multi-Drug Resistance; P-Glycoprotein; Pharmaceutical Preparations; Protein Family; Proteins; Publishing; RNA Interference; Resistance; Role; Series; Specificity; Work; cancer therapy; cell killing; chemotherapeutic agent; cytotoxic; inhibitor/antagonist; member; neoplastic cell

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.

大量的相关基因表达数据已经显示了基因表达之间的联系。 ABC家族蛋白质的关键成员的表达和对许多最常见的 通常使用的抗癌化疗剂。目前的方法来分析直接 多药耐药（MDR）蛋白表达的功能性后果具有 由于缺乏药物抑制剂的特异性，以及可能的重叠， 这些蛋白质在肿瘤细胞发生MDR时的功能作用。细胞实验室 生物学，CCR最近发现了一种化合物，似乎特别是细胞毒性， 过表达MDR-1（ABCB 1）的细胞。使用对应于ABCB 1的完全表征的siRNA 我们现在已经表明，MDR-1的表达确实调节细胞对这种药物的敏感性。 化合物.这项工作现已出版。我们还参与了一项研究， Calcagno和Ambudkar博士（LCB，CCR，NCI）研究ABCG 2在耐药性中的作用。 描述这项工作的手稿已经提交。