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Nat Cell Biol. 2001 Dec;3(12):1124-8.

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

Author information

1
The Burnham Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

The PTEN tumour suppressor and pro-apoptotic gene is frequently mutated 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 found that Egr-1 specifically binds to the PTEN 5' untranslated region, which contains a functional GCGGCGGCG Egr-1-binding site. Inducing Egr-1 by exposing cells to ultraviolet light upregulates expression of PTEN messenger RNA and protein, and leads to apoptosis. egr-1-/- cells, which cannot upregulate PTEN expression after irradiation, are resistant to ultraviolet-light-induced apoptosis. Therefore, Egr-1 can directly regulate PTEN, triggering the initial step in this apoptotic pathway. Loss of Egr-1 expression, which often occurs in human cancers, could deregulate the PTEN gene and contribute to the radiation resistance of some cancer cells.

PMID:
11781575
DOI:
10.1038/ncb1201-1124
[Indexed for MEDLINE]

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