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

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Abstract

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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Acknowledgments

We would like to thank Dr. Lukasz Pulaski for helpful discussions. This work was partially supported by the Project PL0107 “Cellular biosensors for automated monitoring of environmental pollution,” by the START Programme of the Foundation for Polish Science, and by statutory funds from the Institute of Medical Biology.

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  1. Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232, Lodz, Poland

    Iwona Sachrajda & Marcin Ratajewski

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  1. Iwona Sachrajda
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  2. Marcin Ratajewski
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Correspondence to Marcin Ratajewski.

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Communicated by S. Hohmann.

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Sachrajda, I., Ratajewski, M. Mithramycin A suppresses expression of the human melanoma-associated gene ABCB8 . Mol Genet Genomics 285, 57–65 (2011). https://doi.org/10.1007/s00438-010-0586-8

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  • DOI: https://doi.org/10.1007/s00438-010-0586-8

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