Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence

Krones-Herzig, Anja; Adamson, Eileen D.; Mercola, Dan

doi:10.1073/pnas.2628034100

Cited by 111 publications

(104 citation statements)

References 41 publications

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“…Thus, regulation of p53 expression by Egr1 plays a central functional role in p53-dependent growth control in the mouse. 36 Consistent results have been observed in a variety of human cell and tissue systems (Table 1). For example, p53 is mutated in the majority of fresh human glioblastoma and these tumors exhibit near normal levels of Egr1.…”

Section: P53family: P53supporting

confidence: 78%

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

279

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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: P53family: P53supporting

confidence: 78%

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

279

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“…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. Similarly, Egr-1 ablation delays progression of SV40 T-driven mouse prostate adenocarcinomas, without affecting tumor incidence or burden (Abdulkadir et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2008

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Activation of the Raf/MEK/ERK pathway, often by gainof-function mutations of RAS or RAF, is observed in many human cancers. The extracellular signal-regulated kinase (ERK) pathway is required for the proliferation of cancer cell lines harboring activating BRAF or, to a lesser extent, activating RAS mutations. It is still unclear, however, whether the pathway is required in vivo for tumor development, particularly in tumors in which B-Raf is not mutationally activated. During embryonic development, B-Raf is essential for angiogenesis in the placenta. To address the question of whether B-Raf contributed to tumor angiogenesis in vivo we conditionally ablated B-Raf in a model of pancreatic islet carcinoma driven by the functional inactivation of tumor suppressors (RIP1Tag2), which critically depends on angiogenesis for growth. We find that B-Raf is dispensable for the proliferation of tumor cells in culture, but necessary for ERK activation and for the expression of angiogenic factors by tumor cells in vivo and in vitro. In vivo, these defects result in the formation of hollow tumors with decreased vessel density and strongly reduced proliferation. The progression from adenoma to carcinoma is also significantly impaired. Thus, endogenous B-Raf contributes to the development of RIP1Tag2 tumors by supporting the stromal response and tumor progression.

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“…Clarity on this matter remains to be experimentally determined and is necessary to shed further light on the transcriptional regulation of TPα in both the normal and the malignant prostate/breast tissue and potentially in other tissues in which the TXA 2 -TP axis is implicated. Critically, given that Egr1 serves as a master regulator in several key aspects of prostate and breast cancer progression (89,90), investigation of the interplay between WT1 and Egr1 in the regulation of TPα expression through Prm1 within the TBXA2R as a function of tumour grade merits detailed investigation.…”

Section: Role Of Wilms' Tumour 1 In Regulating Tpα Expression In Prosmentioning

confidence: 99%

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

Kinsella

2016

Wilms Tumor

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Copyright: The Author.Licence: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the author and the publisher are explicitly identified and properly acknowledged as the original source. AbstractThe prostanoid thromboxane (TX)A 2 plays a fundamental role in vascular haemostasis and, more recently, is increasingly implicated in various neoplasms including in prostate, breast and bladder cancers, among others. In humans, TXA 2 signals through the TPα and TPβ isoforms of the T prostanoid receptor (TP), two structurally related receptors that display both common, over-lapping but also distinct, isoform-specific physiologic roles. Consistent with this, while TPα and TPβ are encoded by the same gene, the TBXA2R, they are Kinsella 164 differentially expressed due to their transcriptional regulation by distinct promoters where promoter (Prm) 1 regulates TPα expression and Prm3 regulates TPβ. While the clinical evidence for the role of the TXA 2 -TP axis in neoplastic progression is increasing, few studies to date have investigated the role of the individual TPα/TPβ isoforms in human cancer or indeed in most other diseases in which the TXA 2 -TP axis is implicated. Focusing on TPα, this review details the current understanding of the factors regulating its expression and transcriptional regulation through Prm1, including in prostate and breast cancers. Emphasis is placed on the trans-acting transcriptional regulators that bind to cis-elements within the core and upstream regulatory regions of Prm1 under basal conditions and in response to cellular differentiation. A particular focus is placed on the role of the tumour suppressor Wilms' tumour 1 in the regulation of TPα expression through Prm1 in megakaryoblastic cells of vascular origin and in prostate and breast carcinoma cells. Collectively, this review details current knowledge of the factors determining regulation of the TXA 2 -TPα axis and thereby provides a genetic basis for understanding the role of TXA 2 in the progression of certain human cancers.

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Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence

Cited by 111 publications

References 41 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

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

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

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