RNF8 identified as a co-activator of estrogen receptor α promotes cell growth in breast cancer

The ring finger protein 8 (RNF8), a key component of protein complex crucial for DNA-damage response, consists of a forkhead-associated (FHA) domain and a really interesting new gene (RING) domain that enables it to function as an E3 ubiquitin ligase. However, the biological functions of RNF8 in estrogen receptor alpha (ER alpha)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ER alpha in breast cancer cells, and co-activates ER alpha-mediated transactivation. Accordingly, RNF8 depletion inhibits the expression of endogenous ER alpha target genes. Interestingly, our results have demonstrated that RNF8 increases ER alpha stability at least partially if not all via triggering ER alpha monoubiquitination. RNF8 functionally promotes breast cancer cell proliferation. RNF8 is highly expressed in clinical breast cancer samples and the expression of RNF8 positively correlates with that of ER alpha. Up-regulation of ER alpha-induced transactivation by RNF8 might contribute to the promotion of breast cancer progression by allowing enhancement of ER alpha target gene expression. Our study describes RNF8 as a co-activator of ER alpha increases ER alpha stability via post-transcriptional pathway, and provides a new insight into mechanisms for RNF8 to promote cell growth of ER alpha-positive breast cancer. (C) 2017 Elsevier B.V. All rights reserved.