BEX3 Gene and Spice Variants
BEX3 in Neurotrophin Receptor Signaling
Role of BEX3 in Cancer
BEX proteins play differential roles in cancer. BEX1 has been shown to be a tumor suppressor while BEX2 acts as an oncogene (Kazi et al. 2015; Lindblad et al. 2015). There are a few studies describing the involvement of BEX3 in cancer. The human ovarian carcinoma cell line (PA-1) and the mouse teratocarcinoma cell line (F9) express BEX3 (Kim et al. 2004). In PA-1 and F9 cell lines, BEX3 was found to be associated with mitochondria suggesting a role in regulation of mitochondrial function. Breast cancer cell lines express the NGF receptors p75NTR and TRKA, as well as BEX3 (Descamps et al. 2001; Tong et al. 2003) indicating a possible involvement of BEX3 in breast cancer. Overexpression of BEX3 in MDA-MB-231 human breast cancer cells suppressed in vivo tumor formation suggesting that BEX3 acts as tumor suppressor in breast cancer (Tong et al. 2003). Furthermore, BEX3 associates with SMAC (Yoon et al. 2004). SMAC is a mitochondrial protein that induces cytochrome c-dependent caspase activation (Du et al. 2000). Association of BEX3 with SMAC inhibits XIAP-mediated SMAC ubiquitination but promotes TRAIL-induced apoptosis in MCF7 breast cancer cells (Yoon et al. 2004). Thus, in breast cancer BEX3 appears to be a proapoptotic gene.
Role of BEX proteins in human pathophysiology has not been extensively studied. Current studies suggest that BEX3 plays an important role in signaling by the nerve growth factor receptors. BEX3 induces apoptosis by forming multi-protein complexes in response to NGF stimulation, which is required apoptosis. Therefore, BEX3 expression is required for maintaining basal levels of NGF signaling. Involvement of BEX3 in cancer is also evident. BEX3 acts as a tumor suppressor in breast cancer by inducing apoptosis.