Gillet Jean-Pierre, Efferth Thomas, Steinbach Daniel, Hamels Jacques, de Longueville Françoise, Bertholet Vincent, Remacle José
Research Unit of Cellular Biology, University of Namur, Namur, Belgium.
Cancer Res. 2004 Dec 15;64(24):8987-93. doi: 10.1158/0008-5472.CAN-04-1978.
Different mechanisms of drug resistance, including ATP-binding cassette (ABC) transporters, are responsible for treatment failure of tumors. We developed a low-density DNA microarray which contains 38 genes of the ABC transporter gene family. This tool has been validated with three different multidrug-resistant sublines (CEM/ADR5000, HL60/AR, and MCF7/CH1000) known to overexpress either the ABCB1 (MDR1), ABCC1 (MRP1), or ABCG2 (MXR and BCRP) genes. When compared with their drug-sensitive parental lines, we observed not only the overexpression of these genes in the multidrug-resistant cell lines but also of other ABC transporter genes pointing to their possible role in multidrug resistance. These results were corroborated by quantitative real-time reverse transcription-PCR. As the microarray allows the determination of the expression profile of many ABC transporters in a single hybridization experiment, it may be useful as a diagnostic tool to detect drug resistance in clinical samples.
包括ATP结合盒（ABC）转运蛋白在内的不同耐药机制是导致肿瘤治疗失败的原因。我们开发了一种低密度DNA微阵列，其包含ABC转运蛋白基因家族的38个基因。该工具已通过三种不同的多药耐药亚系（CEM/ADR5000、HL60/AR和MCF7/CH1000）进行验证，已知这些亚系过表达ABCB1（MDR1）、ABCC1（MRP1）或ABCG2（MXR和BCRP）基因。与它们的药物敏感亲本系相比，我们不仅在多药耐药细胞系中观察到这些基因的过表达，还观察到其他ABC转运蛋白基因的过表达，这表明它们在多药耐药中可能发挥作用。这些结果通过定量实时逆转录PCR得到了证实。由于该微阵列能够在单次杂交实验中确定多种ABC转运蛋白的表达谱，因此它可能作为一种诊断工具用于检测临床样本中的耐药性。
