BRCA1 in Gene-specific Coordination of Transcription and DNA-Damage Response

摘要

BRCA1 is a tumor suppressor gene for hereditary breast and ovarian cancers. In collaborating with various binding partners, BRCA1 protein participates in multiple cellular functions. Characterization of these binding proteins of BRCA1 is therefore key to the complete understanding of BRCA1's role in tumor suppression. Cofactor of BRCA1 (COBRA1) is a novel BRCA1- interacting protein and shares several functional commonalities with BRCA1 in regulating expression of genes involved various types of cancers. During the past year, we made significant progress in elucidating the role of COBRA1 in breast cancers. By using the xenograft model, we found that COBRA1 reduction led to increased estrogen sensitivity of breast cancer cells and elevated growth potential in the presence of limited amount of estrogen. In addition, we found that COBRA1 reduction in breast cancer cells promoted tumor recurrence after estrogen ablation. Thus, our work uncovered a unique function of COBRA1 in breast cancer. It also provides a solid and logical foundation for exploring a synergistic relationship between BRCA1 and COBRA1 in future studies.