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 TGFb1, 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 TGFb1 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.

B-Raf is required for ERK activation and tumor progression in a mouse model of pancreatic β-cell carcinogenesis

“…Egr-1 can either suppress or enhance tumor development in mouse models and in humans, depending on the molecular context (Baron et al, 2005). Egr-1's tumor suppressor function relies on its ability to induce p53 (Krones- Herzig et al, 2003Herzig et al, , 2005, disabled by SV40T antigen in the RIP1Tag2 model.…”

5q– myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics

“…EGR1 is an early response gene and can mediate cellular responses to mitogens and growth factors. Such activity is typically associated with oncogenes, but interestingly, Egr1 possesses significant tumor-suppressor properties through its ability to directly regulate key target genes, including TGFb1, PTEN and p53 (TPR53) (Baron et al, 2006). Egr1 þ /À or Egr1 À/À mouse embryonic fibroblasts bypass senescence and, therefore, Egr1 was suggested to be an upstream regulator or 'gatekeeper' of p53-dependent growth regulation .…”

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

“…7,36 Furthermore, up-regulation of EGR1 can activate other factors involved in apoptosis. It has been reported that EGR1 can up-regulate the expression level of PTEN directly to activate the pro-apoptotic pathway by binding with the PTEN promoter in 293T human fetal kidney cells 37 and in age-related diseases. 12,13 Similarly, EGR1 can also directly induce the transcription of p53 by binding with the p53 promoter in human melanoma A375-C6 cells during thapsigargin-induced apoptosis.…”