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The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin

Abstract

Recent studies are reviewed indicating that the transcription factor early growth response-1 (Egr1) is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other, suggesting the existence of a functional network of suppressor factors that serve to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr1 is oncogenic in prostate cancer. In the majority of these cancers, PTEN or p53 is inactive. It is suggested that these defects in the suppressor network allow for the unopposed induction of TGFβ1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, and explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods, and targeting methods are discussed.

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Acknowledgements

We acknowledge the support of the USPHS for funding as NIH RO1 67888 (EDA), The US Army Medical Research and Materiel Command DOD, DAMD-17-01-1-0005 and 0165, (EDA), NIH/NCI for UO1 CA084998 (DAM), RO1 CA084107 (DAM), and 1RO1 CA102688 (VB). We thank Connie White for the graphics and formatting.

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Baron, V., Adamson, E., Calogero, A. et al. The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin. Cancer Gene Ther 13, 115–124 (2006). https://doi.org/10.1038/sj.cgt.7700896

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