A role of BRCA1-associated protein BARD1 in oxidative stress response and signaling and proliferation control

Abstract

More than a decade ago, the BRCA1 and BRCA2 genes, responsible for familial breast cancers, were discovered. About 50 percent of women diagnosed with breast cancer have inherited mutations in BRCA1 or BRCA2 that predispose them to breast and ovarian cancer. Although there are several thousand publications concerning analysis of structure, expression, and function of these genes, no treatment methods for breast cancer have been developed that based on the accumulated knowledge. BRCA1 and BRCA2 are large proteins that interact with many other proteins of diverse functions. One particular protein, BARD1, a binding partner of BRCA1, might crucially regulate the tumor suppressor function of BRCA1 and act as a tumor suppressor in its own right. The functions attributed to BARD1 might make it indispensable for cell viability. This might explain why BARD1 mutations are rarely found in cancer, but aberrant truncated forms are overexpressed. Disappointingly, while screening for mutations in the predisposition genes BRCA1 and BRCA2 is now routinely carried out, no treatment methods have been developed that are based on our knowledge of BRCA1 and BRCA2 functions, which leaves mutation carriers without hope for future treatment. It will be interesting how dissection of the functions of BARD1 will open new avenues for cancer treatment. Here we discuss that BARD1 expression can be regulated in a cell cycle dependent way, in a hormone dependent was, and by hypoxia and oxidative stress. Understanding the way how BARD1 is activated will be important the understanding of its role in tumorigenesis and in the search for treatment targets. © 2008 Springer Netherlands.