1. Department of Tumor Surgery, the First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, 277 W. Yanta Road, Xi'an, Shaanxi 710061, China
2. Marriotts Ridge High School, 12100 Woodford Drive, Marriottsville, MD 21104, USA
3. Department of Biochemistry and Molecular Biology, The Catharine Birch McCormick Genomics Center, George Washington University Medical Center, 2300 I Street, Washington DC 20037, USA
4. Department of OB & GYN, the First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, 277 W. Yanta Road, Xi'an, Shaanxi 710061, China
Homeobox genes are known to be critically important in tumor development and progression. The BP1 (Beta Protein 1) gene, an isoform of DLX4, belongs to the Distal-less (DLX) subfamily of homeobox genes and encodes a homeodomain-containing transcription factor. Our studies have shown that the BP1 gene was overexpressed in 81% of primary breast cancer and its expression was closely correlated with the progression of breast cancer. However, the exact role of BP1 in breast has yet to be elucidated. Therefore, it is important to explore the potential transcriptional targets of BP1 via whole genome-scale screening. In this study, we used the chromatin immunoprecipitation on chip (ChIP-on-chip) and gene expression microarray assays to identify candidate target genes and gene networks, which are directly regulated by BP1 in ER negative (ER-) breast cancer cells. After rigorous bioinformatic and statistical analysis for both ChIP-on-chip and expression microarray gene lists, 18 overlapping genes were noted and verified. Those potential target genes are involved in a variety of tumorigenic pathways, which sheds light on the functional mechanisms of BP1 in breast cancer development and progression.
Keywords: BP1, homeoprotein, ChIP-on-chip, breast cancer, ER