Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Mol Genet Genomics. 2011 Jan;285(1):57-65. doi: 10.1007/s00438-010-0586-8. Epub 2010 Nov 3.
The role of the ABCB8 gene in human cells is poorly understood, although it has been suggested to be involved in multidrug resistance in some types of cancers (e.g., melanomas). In this study, the main mechanism of transcriptional regulation of the ABCB8 gene was characterized. EMSA and ChIP assays revealed that the transcription factor Sp1 binds to the ABCB8 core promoter region, and Sp1 consensus elements were crucial for promoter activity in a luciferase reporter gene assay. Mithramycin A, an inhibitor of Sp1 binding, downregulated the expression of ABCB8 (and other ABC genes) in a concentration-dependent manner and sensitized a melanoma cell line to doxorubicin treatment. These findings may have therapeutic applications in at least a subset of melanoma patients.
ABCB8 基因在人类细胞中的作用尚未完全阐明，尽管有研究表明它可能与某些类型癌症（如黑色素瘤）的多药耐药性有关。本研究对 ABCB8 基因的转录调控的主要机制进行了表征。EMSA 和 ChIP 检测显示转录因子 Sp1 结合到 ABCB8 核心启动子区域，Sp1 共识元件对于荧光素酶报告基因检测中的启动子活性至关重要。米托蒽醌 A 是 Sp1 结合的抑制剂，它以浓度依赖的方式下调 ABCB8（和其他 ABC 基因）的表达，并使黑色素瘤细胞系对阿霉素治疗敏感。这些发现至少在一部分黑色素瘤患者中具有治疗应用的潜力。
