The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling

The PTEN tumour suppressor(1) and pro-apoptotic(2) gene is frequently mutat ed in human cancers. We show that PTEN transcription is upregulated by Egr- 1 after irradiation in wild-type, but not egr-1(-/-), mice in vivo. We foun d that Egr-1 specifically binds to the PTEN 5' untranslated region, which c ontains a functional GCGGCGGCG Egr-1-binding site. Inducing Egr-1 by exposi ng cells to ultraviolet light upregulates expression of PTEN messenger RNA and protein, and leads to apoptosis. egr-1(-/-) cells, which cannot upregul ate PTEN expression after irradiation, are resistant to ultraviolet-light-i nduced apoptosis. Therefore, Egr-1 can directly regulate PTEN, triggering t he initial step in this apoptotic pathway. Loss of Egr-1 expression, which often occurs in human cancers, could deregulate the PTEN gene and contribut e to the radiation resistance of some cancer cells.