Brain-Expressed X-linked (BEX) Proteins in Human Cancers

The Brain-Expressed X-linked (BEX) family proteins are comprised of five human proteins including BEX1, BEX2, BEX3, BEX4 and BEX5. BEX family proteins are expressed in a wide range of tissues and are known to play a role in neuronal development. Recent studies suggest a role of BEX family proteins in cancers. BEX1 expression is lost in a subgroup of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Expression of BEX1 controls cell surface receptor signaling and restores imatinib response in resistant cells. BEX2 is overexpressed in a group of breast cancer patients and also in gliomas. Increased BEX2 expression led to enhanced NF-κB signaling as well as cell proliferation. Although BEX2 acts as tumor promoter in a subset of breast cancer, BEX3 expression displayed an opposite role. Overexpression of BEX3 resulted in inhibition of tumor formation in breast cancer mouse xenograft models. The role of BEX4 and BEX5 in cancer has not yet been defined. Collectively this suggests that BEX family members have distinct roles in cancers. While BEX1 and BEX3 act as tumor suppressors, BEX2 seems to act as an oncogene.