%0 Journal Article
%T BEX2 has a functional interplay with c-Jun/JNK and p65/RelA in breast cancer
%A Ali Naderi
%A Ji Liu
%A Luke Hughes-Davies
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-111
%X We found a marked induction of BEX2 promoter by c-Jun and p65/RelA using luciferase reporter assays in MCF-7 cells. Furthermore, we confirmed the binding of c-Jun and p65/RelA to the BEX2 promoter using a chromatin immunoprecipitation assay. Importantly, transfections of c-Jun or p65/RelA in MCF-7 cells markedly increased the expression of BEX2 protein. Overall, these results demonstrate that BEX2 is a target gene for c-Jun and p65/RelA in breast cancer. These findings were further supported by the presence of a strong correlation between BEX2 and c-Jun expression levels in primary breast tumors. Next we demonstrated that BEX2 has a feedback mechanism with c-Jun and p65/RelA in breast cancer. In this process BEX2 expression is required for the normal phosphorylation of p65 and I¦ÊB¦Á, and the activation of p65. Moreover, it is necessary for the phosphorylation of c-Jun and JNK kinase activity in breast cancer cells. Furthermore, using c-Jun stable lines we showed that BEX2 expression is required for c-Jun mediated induction of cyclin D1 and cell proliferation. Importantly, BEX2 down-regulation resulted in a significant increase in PP2A activity in c-Jun stable lines providing a possible underlying mechanism for the regulatory effects of BEX2 on c-Jun and JNK.This study shows that BEX2 has a functional interplay with c-Jun and p65/RelA in breast cancer. In this process BEX2 is a target gene for c-Jun and p65/RelA and in turn regulates the phosphorylation/activity of these proteins. These suggest that BEX2 is involved in a novel feedback mechanism with significant implications for the biology of breast cancer.We have previously demonstrated that BEX2, a member of Brain Expressed X-linked gene family, is differentially expressed in breast tumors and BEX2 expression predicts the response to tamoxifen therapy [1]. Although BEX2 shows a relatively higher expression in 15% of breast cancers, this gene is expressed in the majority of breast tumors and breast cancer cell lines
%U http://www.molecular-cancer.com/content/9/1/111