Transcriptional Regulation of EGR1 by EGF and the ERK Signaling Pathway in Prostate Cancer Cells

Gregg, Jay M.; Fraizer, Gail

doi:10.1177/1947601911431885

Cited by 59 publications

(56 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently it has been demonstrated that EGR1 expression in prostate cancer cells is mediated by an ERK signaling cascade. 22 Interestingly ERK1/2 pathway was found to be deregulated in the AR-expressing CRPC cells in the present study (data not shown). It is likely that "AR gain" deregulates ERK1/2 pathway, that in turn contributes to a decrease in the EGR1 expression.…”

Section: Discussionsupporting

confidence: 50%

A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

Jacob

Nayak

Kakar

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Telomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit-hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity. Existing data suggest that hTERT expression and telomerase activity are positively regulated by androgenic stimuli in androgendependent prostate cancer (ADPC) cells. A part of the present study reaffirmed this by demonstrating a decline in the hTERT expression and telomerase activity on "loss of AR" in ADPC cells. The study further addressed 2 unresolved queries, i) whether AR-mediated signaling is of any relevance to hTERT expression in castration-resistant prostate cancer (CRPC) and ii) whether this signaling involves EGR1. Our data suggest that AR-mediated signaling negatively regulates hTERT expression in CRPC cells. Incidental support for the possibility of EGR1 being a regulator of hTERT expression in PCa was provided by i) immunolocalization of hTERT and EGR1 proteins in the same cell type (secretory epithelium) of PCa and BPH tissues; ii) significantly (p< 0.001) higher levels of both these proteins in CRPC (PC3 and DU145), compared with ADPC (LNCaP) cells. A direct evidence for the role of EGR1 in hTERT expression was evident by a significant (p<0.0001) decrease in the hTERT transcript levels in the EGR1-silenced CRPC cells. Further, "gain of AR" led to a significant reduction in the levels of hTERT and EGR1 in CRPC cells. However, restoration of EGR1 levels prevented the decline in the hTERT transcript levels in these cells. Taken together, our data indicate that AR regulates the expression of EGR1, which in turn acts as a positive regulator of hTERT expression in CRPC cells. Thus, AR exerts an inhibitory effect on hTERT expression and telomerase activity by modulating EGR1 levels in CRPC cells.

show abstract

Section: Discussionsupporting

confidence: 50%

A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

Jacob

Nayak

Kakar

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…S6). Previous studies of the EGR1 promoter demonstrated that the ELK-1-and SRF-binding sites within the proximal promoter region are critical for promoter activation in response to various stimuli, including thrombin and EGF (25,(31)(32)(33)(34). EGR1 promoter activity was synergistically increased in cells transfected with WT-STAT3 in response to EGF plus TRAP.…”

Section: Egfr/par-1 Cross-talk Regulates Stat3 Activationmentioning

confidence: 96%

“…4D). Because MAPK signaling pathways are active in this context, residual promoter activity of the distal GAS mutant is likely due to EGF-induced activation of serum-response elements within the proximal promoter (31,35). Next, we measured the DNA binding activity of STAT3 in response to EGF plus TRAP treatment using a DNA-binding ELISA.…”

Section: Egfr/par-1 Cross-talk Regulates Stat3 Activationmentioning

confidence: 99%

STAT3-mediated Coincidence Detection Regulates Noncanonical Immediate Early Gene Induction

Waitkus

Chandrasekharan

Willard

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…EGF signaling is proposed to participate in the pathogenesis or maintenance of several types of human cancers of an epithelial origin (13). In prostate cancer cells, EGFR ligands are frequently elevated and EGFR itself is commonly overexpressed (14). Furthermore, EGFR expression increases during progression to a hormone-resistant stage (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Role of GLI-1 in epidermal growth factor-induced invasiveness of ARCaPE prostate cancer cells

et al. 2013

View full text Add to dashboard Cite

Abstract. Epidermal growth factor (EGF) signaling and Hedgehog (HH) signaling are both involved in prostate cancer (PCa) progression, yet the mechanisms through which these two pathways are synergistically linked require elucidation. In the present study, we aimed to ascertain how EGF and the HH signaling transcription factor GLI-1 are linked in prostate cancer invasiveness. ARCaP human prostate cancer cells, which included ARCaP E and ARCaP M cells, were used as a model in the present study. The expression of EGF receptor (EGFR) and the HH signaling transcriptional factor GLI-1 were detected in ARCaP E cells by immunofluorescence, and the ARCaP E cells were treated with human recombinant EGF protein (hrEGF) for 4 consecutive days in vitro. Transwell invasion assays were performed in the ARCaP E cells following treatment with DMSO (vehicle control), hrEGF, GATN61 (GLI-1-specific inhibitor), hrEGF plus GANT61 and in the ARCaP M cells. The expression of phosphorylated extracellular signal regulated kinase (p-ERK), total ERK and GLI-1 was detected by western blotting in ARCaP E cells at different timepoints following treatment with hrEGF. The expression of EGFR and GLI-1 was detected in ARCaP E cells, which exhibited a cobblestone-like morphology, while after treatment with hrEGF, the cell morphology was altered to a spindle-shaped mesenchymal cell morphology. Transwell invasion assays demonstrated that hrEGF dramatically enhanced the invasive capability of the ARCaP E cells (P<0.05). Additionally, western blot assay demonstrated that the expression levels of p-ERK and GLI-1 in ARCaP E cells increased in a time-dependent manner after treatment with hrEGF (P<0.05); however, the expression levels of total ERK in the cells remained relatively unchanged. It also demonstrated that the GLI-1 inhibitor GANT61 could reverse the enhanced invasive effect induced by EGF in ARCaP E cells (P<0.05). Our preliminary in vitro study showed that EGF signaling may increase the invasive capability of ARCaP E human prostate cancer cells via upregulation of p-ERK and the HH signaling transcriptional factor GLI-1. Additionally, this enhanced cell invasive effect was reversed by a GLI-1-specific inhibitor in vitro. Consequently, it indicates that both EGF and HH signaling are synergistically involved in the progression of human prostate cancer ARCaP cells, and GLI-1 may be one of the important effectors, which is activated by EGF downstream signaling, to promote the invasiveness of ARCaP E prostate cancer cells.

show abstract

Transcriptional Regulation of EGR1 by EGF and the ERK Signaling Pathway in Prostate Cancer Cells

Cited by 59 publications

References 55 publications

A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

STAT3-mediated Coincidence Detection Regulates Noncanonical Immediate Early Gene Induction

Role of GLI-1 in epidermal growth factor-induced invasiveness of ARCaPE prostate cancer cells

Contact Info

Product

Resources

About