EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK.

EGR2 plays a key role in the PTEN-induced apoptotic pathway. Using adenovirus-mediated gene transfer to 39 cancer cell lines, we found that EGR2 could induce apoptosis in a large proportion of these lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9. Analysis by cDNA microarray and subsequent functional studies revealed that EGR2 directly transactivates expression of BNIP3L and BAK. Our results helped to clarify the molecular mechanism of the apoptotic pathway induced by PTEN-EGR2, and suggested that EGR2 may be an excellent target molecule for gene therapy to treat a variety of cancers.