BRCA1 directly modulates gene expression required for estrogen biosynthesis: a possible mechanism of tissue-specific tumor suppression

Excerpt

Mutations in the tumor suppressor gene BRCA1 are associated with an elevated risk of breast and ovarian cancer. The tissue-specific nature of BRCA1 mutation-associated tumors stands in stark contrast to the diverse array of nuclear functions mediated by the wild-type BRCA1. These functions include regulation of transcription and the DNA damage response. While the DNA repair function of BRCA1 clearly contributes to overall genetic stability, loss of BRCA1 function in DNA repair, a process that is universally important to all cell types in both genders, cannot easily explain why BRCA1 mutations predominantly affect breast and ovary, two major estrogen-responsive tissues in women. We hypothesize that BRCA1 confers tissue-specific tumor suppression by directly modulating expression of a set of breast-cancer-related genes. …