ScienceVEGF

VEGF and BRCA-1 in breast cancer

The BRCA-1 gene is a well-known breast cancer susceptibility gene that normally plays a role in repairing breaks in DNA. However, when BRCA-1 is mutated, this repair function becomes disabled, leading to DNA replication errors, increased genomic instability and ultimately cancer. Indeed, individuals with the BRCA-1 mutation have an increased risk of developing breast or ovarian cancer.

In 2002, Kawai and colleagues demonstrated that VEGF expression and secretion are controlled by a direct interaction involving BRCA-1 protein and the ER. Using normal breast tissue and breast cancer cell lines, the investigators showed that normal BRCA-1 protein suppressed the VEGF promoter (a proximal segment of DNA involved in turning on transcription of a gene) via the ER-α subunit and also regulated the secretion of VEGF from the cell. By contrast, mutated BRCA-1 was not able to suppress VEGF expression, leading to the conclusion that mutations in BRCA-1 could indirectly promote tumourigenesis in part by causing dysregulation of VEGF function.¹⁰