T. Virolle et al., The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling, NAT CELL BI, 3(12), 2001, pp. 1124-1128
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.