Direct and Coordinate Regulation of ATP-binding Cassette Transporter Genes by Myc Factors Generates Specific Transcription Signatures That Significantly Affect the Chemoresistance Phenotype of Cancer Cells

摘要: Increased expression of specific ATP-binding cassette (ABC) transporters is known to mediate the efflux chemotherapeutic agents from cancer cells. Therefore, establishing how ABC transporter genes are controlled at their transcription level may help provide insight into role these multifaceted in malignant phenotype. We have investigated gene a large neuroblastoma data set 251 tumor samples. Clustering analysis demonstrated strong association between differential patterns samples and amplification MYCN oncogene, suggesting correlation with function. Using profiling chromatin immunoprecipitation studies, we show that oncoprotein coordinately regulates genes, by acting as either an activator or repressor. Finally, extend notions c-MYC showing it can also regulate same other cells through similar dynamics. Overall our findings MYC-driven molecular mechanisms contribute coordinate transcriptional regulation thus affecting global drug efflux.