Increased Expression of Early Growth Response-1 Messenger Ribonucleic Acid in Prostatic Adenocarcinoma

Thigpen, Anice E.; Cala, Kristine M.; Guileyardo, Joseph M.; Molberg, Kyle; McConnell, John D.; Russell, David W.

doi:10.1016/s0022-5347(01)66361-4

Cited by 51 publications

(42 citation statements)

References 12 publications

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“…13,28 Paradoxically, increased expression of Egr1 is consistently observed in prostate cancer where growing evidence indicates that Egr1 is oncogenic. Russell and co-workers 55 observed that Egr1 mRNA levels were elevated in 12 of 12 cases of organ-confined prostate cancer but not in breast or ovarian cancers, or in rapidly dividing rat ventral prostate cells. Egr1 mRNA was detected in epithelial and stromal cells at tumor margins but not in lymph node metastases.…”

Section: Egr1-induced Oncogenesis Of Prostate Cancermentioning

confidence: 98%

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

Bar-On

Adamson

Calogero³

et al. 2005

Cancer Gene Ther

318

278

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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.

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Section: Egr1-induced Oncogenesis Of Prostate Cancermentioning

confidence: 98%

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

Bar-On

Adamson

Calogero³

et al. 2005

Cancer Gene Ther

318

278

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“…11,12 Loss of expression of an EGR1 repressor protein, NGF-1A-binding protein (NAB2), may also contribute to elevated EGR1 levels found in prostate tumors. 13 Functional studies using antisense EGR1 RNA reduced cell proliferation, colony formation, and growth in soft agar in prostate cancer cells, suggesting that EGR1 is necessary for the transformed tumor phenotype.…”

Section: Introductionmentioning

confidence: 99%

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

Gregg

Fraizer

2011

Genes & Cancer

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The early growth response gene 1, EGR1, is an important transcriptional regulator and acts as the convergent point between a variety of extracellular stimuli and activation of target genes. Unlike other tumor types, prostate tumors express high levels of EGR1 relative to normal tissues. However, the mechanism of EGR1 regulation in prostate tumor cells is unknown. As EGR1 expression and epidermal growth factor (EGF) signaling are frequently upregulated in prostate tumors, we tested the hypothesis that EGF induces EGR1 expression in prostate cancer cells. Using RT-PCR to quantify EGR1 transcripts, we found that EGF induced EGR1 expression in a dose-and time-dependent manner and the ERK pathway inhibitor, PD98059, abrogated the EGF-mediated EGR1 response in LNCaP and PC3 cells. Analysis of the EGR1 promoter using deletion constructs identified an EGF-responsive region in the proximal promoter (-771 to -245 bp) containing 3 potential serum response element (SRE) sites. In vivo chromatin immunoprecipitation assays demonstrated that Elk-1 binding at the SRE sites of the EGR1 promoter was enhanced by EGF treatment in PC3 cells. Overexpression of Elk-1 was sufficient to activate the EGF-responsive region of EGR1 promoter in PC3 cells and, similarly, a dominant-negative Elk-1 suppressed EGR1 promoter activity. Taken together, these results demonstrate for the first time that EGR1 expression in PC3 cells is mediated through an EGF-ERK-Elk-1 signaling cascade.

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“…Among the 11 highest upregulated transcripts in TAHN tissues were EGR-1, c-Fos, and the growth/differentiation factor 15 (GDF-15), also called macrophage inhibitory cytokine-1 (MIC1). EGR-1 has been strongly implicated in prostate cancer (13)(14)(15)(16)(17)(18)(19)(20) and regulates multiple target genes that in turn have a potential role in prostatic carcinogenesis and progression, such as epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF), and human telomerase reverse transcriptase (hTERT), thereby regulating a spectrum of cellular responses, including growth and growth arrest, survival and apoptosis, and differentiation and transformation (40,41). The involvement of c-Fos as part of the transcription factor activator protein 1 (AP-1) that is activated downstream of many growth factors is supported by a large body of literature on oncogenesis and metastasis (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…~2.8-fold up-regulated compared to cancer-free tissues, as defined in Table III). Early growth response protein 1 (EGR-1) represents the transcript most up-regulated (8.92-fold) in TAHN tissues and has been previously implicated in prostate tumorigenesis (13)(14)(15)(16)(17)(18)(19)(20). Its expression in tumor tissue was 9.27-fold (Table IV).…”

Section: Microarray Expression Analysismentioning

confidence: 99%

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

Haaland

Heaphy²,

Butler³

et al. 2009

Int J Oncol

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Abstract. Field cancerization denotes the occurrence of aberrant cells in tumor adjacent histologically normal tissues (TAHN). To characterize field cancerization in prostate cancer, we used RNA from paired patient tumor and TAHN tissues excised at 1 cm from the tumor margin and subjected them to microarray expression analysis comparative to RNA from normal cancer-free prostatic tissues. Eleven novel transcripts were significantly up-regulated in TAHN tissues and also in tumors. Expression of early growth response protein 1, tristetraprolin, testican, and fatty acid synthase, mutually up-regulated at different levels in tumors and TAHN tissues was confirmed by quantitative reverse transcriptase PCR in the experimental and in an independent validation set. This study offers proof of expressional changes in field cancerized prostatic TAHN tissues at defined distances from tumor margins. Markers of field cancerized prostatic tissues could be early diagnostic indicators in biopsies after abnormal prostate-specific antigen and digital rectal examination and independent of cancerous histology and/or early targets for chemo-preventive intervention in pre-malignant disease.

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Increased Expression of Early Growth Response-1 Messenger Ribonucleic Acid in Prostatic Adenocarcinoma

Abstract: Early growth response-1, a nuclear transcription factor, is implicated in the growth and invasion of intraprostatic cancers.

Cited by 51 publications

References 12 publications

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

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

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

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

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