EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis

Svaren, John; Ehrig, Torsten; Abdulkadir, Sarki A.; Ehrengruber, Markus U.; Watson, Mark A.; Milbrandt, Jeffrey

doi:10.1074/jbc.m005220200

Cited by 166 publications

(143 citation statements)

References 57 publications

(55 reference statements)

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“…This observation was initially reported by Svaren and colleagues (16) and subsequently confirmed by others (11,17). The importance of this finding is related to the rapid and strong EGR1 increase induced by growth factors, mitogens, cytokines, environmental and mechanical stresses, and DNA damage.…”

Section: Structure and Regulation Of The Cdkn1c Genesupporting

confidence: 63%

p57Kip2 and Cancer: Time for a Critical Appraisal

Borriello

Caldarelli

Bencivenga

et al. 2011

Molecular Cancer Research

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p57Kip2 is a cyclin-dependent kinase inhibitor belonging to the Cip/Kip family, which also includes p21Cip1 and p27Kip1. So far, p57Kip2 is the least-studied Cip/Kip protein, and for a long time its relevance has been related mainly to its unique role in embryogenesis. Moreover, genetic and molecular studies on animal models and patients with Beckwith-Wiedemann syndrome have shown that alterations in CDKN1C (the p57Kip2 encoding gene) have functional relevance in the pathogenesis of this disease. Recently, a number of investigations have identified and characterized heretofore unexpected roles for p57Kip2. The protein appears to be critically involved in initial steps of cell and tissue differentiation, and particularly in neuronal development and erythropoiesis. Intriguingly, p27Kip1, the Cip/Kip member that is most homologous to p57Kip2, is primarily involved in the process of cell cycle exit. p57Kip2 also plays a critical role in controlling cytoskeletal organization and cell migration through its interaction with LIMK-1. Furthermore, p57Kip2 appears to modulate genome expression. Finally, accumulating evidence indicates that p57Kip2 protein is frequently downregulated in different types of human epithelial and nonepithelial cancers as a consequence of genetic and epigenetic events. In summary, the emerging picture is that several aspects of p57Kip2's functions are only poorly clarified. This review represents an appraisal of the data available on the p57Kip2 gene and protein structure, and its role in human physiology and pathology. We particularly focus our attention on p57Kip2 changes in cancers and pharmacological approaches for modulating p57Kip2 levels. Mol Cancer Res; 9(10); 1269–84. ©2011 AACR.

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Section: Structure and Regulation Of The Cdkn1c Genesupporting

confidence: 63%

p57Kip2 and Cancer: Time for a Critical Appraisal

Borriello

Caldarelli

Bencivenga

et al. 2011

Molecular Cancer Research

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“…Further evidence for a role of Egr1 in oncogenesis was provided by experiments using specific high-affinity Egr1 antisense oligonucleotides. [59][60][61] It was shown that in a series of mouse and human prostate cancer cells, Egr1 antisense inhibited cell proliferation, colony formation, and growth in soft agar, 63 Interestingly, several genes identified in this screen are associated with neuroendocrine differentiation, which is known to occur frequently in murine prostate cancer. Another Affymetrix microarray analysis compared mouse prostate cancer cells TRAMP-C2 in the presence or absence of Egr1 antisense.…”

Section: Egr1-induced Oncogenesis Of Prostate Cancermentioning

confidence: 99%

“…[73][74][75] An important feature of the suppressor network in prostate tumors is Egr1-induced TGFb1. 61,63,64 TGFb1 has diverse roles and may have the net effect of promoting the progression of prostate cancer (reviewed in Albrecht et al 72 and Zheng et al 73 ). TGFb1 may also facilitate detachment and metastasis.…”

Section: Egr1-induced Oncogenesis Of Prostate Cancermentioning

confidence: 99%

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

326

281

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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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“…The EBS-GFP reporter plasmid was constructed by subcloning the promoter sequence into the AseI-NheI cloning sites. Adenoviral construct expressing EGR-1 was a gift from Dr Jeffrey Milbrandt (Svaren et al, 2000).…”

Section: Plasmid Constructsmentioning

confidence: 99%

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

et al. 2009

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In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/ lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1.

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EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis

Cited by 166 publications

References 57 publications

p57Kip2 and Cancer: Time for a Critical Appraisal

p57Kip2 and Cancer: Time for a Critical Appraisal

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

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

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