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

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...

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Bibliographic Details
Published in:Molecular genetics and genomics : MGG 2011, Vol.285 (1), p.57-65
Main Authors: Sachrajda, Iwona, Ratajewski, Marcin
Format: Article
Language:English
Subjects:
ABCB8
Animal Genetics and Genomics
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - antagonists & inhibitors
ATP-Binding Cassette Transporters - genetics
Biochemistry
Biomedical and Life Sciences
Cell Line, Tumor
Cloning
Down-Regulation - drug effects
Down-Regulation - genetics
Doxorubicin - pharmacology
Drug Resistance, Neoplasm - drug effects
Drug Resistance, Neoplasm - genetics
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Neoplastic - drug effects
Genes
Genetic testing
Genomics
Human Genetics
Humans
Life Sciences
Melanoma
Melanoma - genetics
Microbial Genetics and Genomics
Mithramycin A
Original Paper
Plant Genetics and Genomics
Plicamycin - analogs & derivatives
Plicamycin - pharmacology
Promoter
Promoter Regions, Genetic - drug effects
Skin Neoplasms - genetics
Sp1
Sp1 Transcription Factor - antagonists & inhibitors
Sp1 Transcription Factor - metabolism
Transcription factors
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Summary: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.
ISSN:1617-4615
1617-4623
DOI:10.1007/s00438-010-0586-8