Mithramycin A suppresses expression of the human melanoma-associated gene ABCB8

被引:0
作者
Iwona Sachrajda
Marcin Ratajewski
机构
[1] Institute of Medical Biology,Laboratory of Transcriptional Regulation
[2] Polish Academy of Sciences,undefined
来源
Molecular Genetics and Genomics | 2011年 / 285卷
关键词
Promoter; Sp1; Mithramycin A; Melanoma;
D O I
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学科分类号
摘要
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.
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页码:57 / 65
页数:8
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