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http://dx.doi.org/10.5483/BMBRep.2013.46.2.202

Egr-1 regulates the transcription of the BRCA1 gene by etoposide  

Shin, Soon Young (SMART Institute of Advanced Biomedical Science, Department of Biomedical Science and Technology, Konkuk University)
Kim, Chang Gun (SMART Institute of Advanced Biomedical Science, Department of Biomedical Science and Technology, Konkuk University)
Lee, Young Han (SMART Institute of Advanced Biomedical Science, Department of Biomedical Science and Technology, Konkuk University)
Publication Information
BMB Reports / v.46, no.2, 2013 , pp. 92-96 More about this Journal
Abstract
The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at -1031, -1005, and -385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1 gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1 promoter activity. We conclude that Egr-1 targets the BRCA1 gene in HeLa cells exposed to etoposide.
Keywords
BRCA1; DNA damage; Egr-1; Etoposide; Promoter activation;
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