An Isoform of Homeobox Gene DLX4 Transcriptionally Represses BRCA1 Expression in Breast Cancer Cells

There has been growing evidence that an isoform of the DLX4 homeobox gene, known as Beta protein 1 (BP1), plays an essential role in breast cancer development and progression through transcriptional regulation of other genes that function as oncogenes or tumor suppressors. BRCA1 is a tumor repressor gene that maintains genomic integrity of the cell via several pathways including DNA repair and apoptosis. Recent studies indicate the loss of BRCA1 expression as a result of its mutation in inherited breast cancers. Reduced expression of BRCA1, however, is seen in sporadic breast cancer cases, suggesting a down-regulation of BRCA1 expression. Bioinformatics analysis has revealed that BP1 could potentially bind to the first intron of BRCA1. Subsequent CHIP and EMSA experiments have confirmed this binding. In this study, we sought to investigate whether BP1 negatively regulates BRCA1 by directly binding to its first intron in ER- and ER+ breast cancer cells using a luciferase reporter gene. Results from our experiments showed that BP1 down-regulates BRCA1 in ER- cell lines. Given that ER- breast cancers are more difficult to treat with the therapies available for ER+ breast cancers, targeting BP1 to provide treatment and prevention for ER- breast cancer patients could be promising.

Author

• Alani, Dowser Haris

Language

• en

Date created

• 2009

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Biochemistry and Molecular Biology

Degree

• M.S.

Advisor

• Fu, Sidney

Committee Member(s)

• Hammel, Neil

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/b5644r577