The role of BRCA1-IRIS in ovarian cancer formation, drug resistance and progression

The BRCA1-IRIS protein was identified in 2004 [1] and later found to be frequently upregulated in multiple sporadic tumor types, including breast and ovarian cancers [2, 3]. In ovarian cancer samples, BRCA1-IRIS expression increases with tumor progression together with survivin [3]. This trend was positively correlated with significant decrease in the level of total FOXO1 and FOXO3a and increase in the phosphorylated form of these proteins and their cytoplasmic sequestration (Figure 1). BRCA1-IRIS overexpression also impacted negatively on the expression of PTEN, which is a potent inhibitor of AKT [3]. As a consequence, loss of PTEN function led to activation of the phosphoinositide 3-kinase (PI3K)-AKT1/2 pathway in BRCA1-IRIS overexpressing cells, which stimulated their growth, survival and drug (e.g., cisplatin) resistance (Figure 1). These data of BRCA1-IRIS and associated oncogenic pathways, has caused great interest in elevated BRCA1-IRIS expression as a biomarker for ovarian cancer early lesions.