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.
Unoki
Motoko
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japam.
Nakamura
Yusuke
Y
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002463:Cell Membrane Permeability; D003574:Cytochrome c Group / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020169:Caspases