The Transcription Factor EGR-1 Suppresses Transformation of Human Fibrosarcoma HT1080 Cells by Coordinated Induction of Transforming Growth Factor-β1, Fibronectin, and Plasminogen Activator Inhibitor-1

Liu, Chaoting; Yao, Jin; Belle, Ian de; Huang, Ruo‐Pan; Adamson, Eileen D.; Mercola, Dan

doi:10.1074/jbc.274.7.4400

Cited by 107 publications

(92 citation statements)

References 70 publications

(72 reference statements)

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“…18 Integrin binding leads to activation of the antiapoptotic pathway Akt via activation of FAK. 18 As described earlier, expression of Egr1 in HT1080 human fibrosarcoma cells results in increased secretion of functional fibronectin 7,13 and activation of FAK. 45 Activated Akt is a major modulator of apoptosis at several levels (reviewed in Ruoslahti 18 and Kishimoto et al 47 ) (Figure 1).…”

Section: P53-pten Interactionsmentioning

confidence: 68%

“…A number of additional studies have documented functional TGFb1 expression in correlation with or following expression of Egr1 in other cells types as well as in vivo (Table 1). In addition to HT1080 cells, this suppression mechanism has been observed in human glioblastoma cells 7 and in the mouse. 8 In connective tissue cells, TGFb1-induced fibrosis in a variety of settings may also be attributed to Egr1.…”

Section: Tgfb1mentioning

confidence: 92%

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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

325

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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Section: P53-pten Interactionsmentioning

confidence: 68%

Section: Tgfb1mentioning

confidence: 92%

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

325

281

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“…We confirmed that E2F-1 protein levels in M1E2F-1/Egr-1 cells are similar to M1E2F-1 cells following IL-6 treatment, yet regulation of all the parameters of cell cycle control examined is consistent with the observed growth arrest. The restoration of induction of TGF-b and p35 (data not shown), two putative Egr-1 target genes that are negative regulators of proliferation (Liu et al, 1999;Chen et al, 2004), to parental cell levels and downregulation of c-Myc, a positive regulator of cell cycle progression that remains elevated in IL-6-treated M1E2F-1 cells, takes place in IL-6-treated M1E2F/ Egr-1 cells. These changes may counteract the effect of continued expression of E2F-1; blocking expression of TGF-b and p35, separately and together, should give further insights into the regulation of the cell cycle during myeloid differentiation.…”

Section: Discussionmentioning

confidence: 93%

“…Egr-1 acts as a growth stimulator in human prostate tumors, but behaves as a tumor suppressor in other cells (Liu et al, 1999;Baron et al, 2003;Shafarenko et al, 2005). Egr-1, a macrophage differentiation primary response gene, has been shown to be essential for and to restrict differentiation along the macrophage lineage (Nguyen et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Egr-1 abrogates the E2F-1 block in terminal myeloid differentiation and suppresses leukemia

2007

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“…Target genes of Egr-1 that are negative regulators of cell growth, including p35 and TGF-b, 18,19 were also analyzed. Although no apparent differences were observed in the expression of TGF-b between any of the cell lines, the expression of p35 was altered.…”

Section: Proliferation and Cell Cycle Analysis Of M1myb/egr-1 Cellsmentioning

confidence: 99%

Leukemia suppressor function of Egr-1 is dependent on transforming oncogene

2008

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We have shown that deregulated expression of either c-Myb or E2F-1 blocks terminal differentiation of M1 myeloid leukemia cells at the blast stage, whereas deregulated c-Myc blocks differentiation at the intermediate stage. Each of these oncogenes potentiates M1 leukemia in vivo. The zinc-finger transcription factor Egr-1 abrogates the block in M1 terminal differentiation imparted by oncogenic c-Myc or E2F-1, suppressing their leukemia-promoting function in nude mice. In this study, we asked whether Egr-1 also abrogates the block in terminal differentiation and suppresses leukemia imparted by deregulated c-Myb. Interestingly, the ectopic expression of Egr-1 in M1 cells expressing deregulated c-Myb only partially abrogated the block in terminal differentiation and did not suppress the leukemic phenotype. Two important implications from these data are that the leukemia suppressor function of Egr-1 is not directly related to how early the transforming oncogene blocks the differentiation program and that the tumor suppressor function of Egr-1 is dependent on the specific oncogene. Egr-1 is dominant to c-Myc-and E2F-1-, but not to c-Myb-, driven leukemia. These findings extend the notion that the molecular nature of genetic lesions responsible for leukemia determines the effectiveness of any given tumor suppressor.

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The Transcription Factor EGR-1 Suppresses Transformation of Human Fibrosarcoma HT1080 Cells by Coordinated Induction of Transforming Growth Factor-β1, Fibronectin, and Plasminogen Activator Inhibitor-1

Cited by 107 publications

References 70 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

Egr-1 abrogates the E2F-1 block in terminal myeloid differentiation and suppresses leukemia

Leukemia suppressor function of Egr-1 is dependent on transforming oncogene

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