The roles of SRA1 gene in breast cancer

Abstract

The Steroid receptor RNA activator (SRA) gene has been implicated in estrogen receptor signaling pathw ay. First identified as a RNA coregulator, SRA had been shown to increase steroid receptor activity. SRA RNA exp ression is altered during breast tumorigenesis and its molecul ar role in underscoring these events has been sugge sted. The subsequent identification of molecules capable of b inding SRA, including RNA helicase p68, SRA stem-loop interacting RNA binding protein (SLIRP), and steroi dogenic factor 1 (SF1) indicates SRA function is no t exclusively limited to modulate steroid receptor activity. A re cent genome-wide expression analysis by depleting SRA in cancer cells has further expanded our understanding of a b roader biological role played by SRA. In addition, several RNA isoforms have been found to encode an endogenous protein (SRAP), which is well conserved among Chordata. Interestingly, SRAP also modulates steroid receptor activity and functions as a co-regulator in estrog en receptor signaling. The recent observation that a higher exp ression of SRAP protein is associated with poorer s urvival in breast cancer patients treated with tamoxifen, highlights the potential relevance of this protein in cancer. Together, the SRA1 gene encodes both functional RNA and protein (SRAP) products, making it a unique member amongst the growing population of steroid receptor co-regulators.