Egr-1 inhibits apoptosis during the UV response: correlation of cell survival with Egr-1 phosphorylation

Huang, Ruo‐Pan; Fan, Yi; deBelle, Ian; Ni, Zhengyu; Matheny, Wynette; Adamson, Eileen D.

doi:10.1038/sj.cdd.4400322

Cited by 61 publications

(72 citation statements)

References 32 publications

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“…The role of phosphorylation of Egr-1 remains controversial (Cao et al, 1993;Jain et al, 1996;Huang et al, 1998;Kamimura et al, 2004). We recently observed that curcumin reduced the level of phosphorylation of Egr-1, which was mimicked by a specific MEK inhibitor (data not shown here).…”

Section: Discussionmentioning

confidence: 98%

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

2005

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High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and sitedirected mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

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Section: Discussionmentioning

confidence: 98%

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

2005

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“…We have also described a series of stable transfected Egr1 clones (19). We used the clone with the maximum expression of Egr1, termed E9, to isolate and identify in vivo Egr1 target genes.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Cloning and Characterization of a New Growth Suppressor Protein TOE1 as a Direct Target Gene of Egr1

Belle¹,

Wu²,

Sperandio³

et al. 2003

Journal of Biological Chemistry

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Egr1, an immediate early transcription factor, responds to diverse stimuli and affects gene transcription to accomplish its biological effects. One important effect of Egr1 expression is to decrease the growth and tumorigenic potential of several tumor cell types. To identify important Egr1 target genes, we have adapted a methodology involving formaldehyde-induced protein-DNA cross-linking, chromatin immunoprecipitation, and multiplex PCR. Using this approach, we report the cloning of a new Egr1 target gene that is able to account, at least in part, for the growth inhibitory activity of Egr1. We have named this new protein TOE1 for target of Egr1.

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“…In addition, EGR-1 is a nuclear phosphoprotein (59), but the biological significance of this modification is unknown. Some reports suggest that the phosphorylated forms of EGR-1 are bound to DNA more efficiently than the non-phosphorylated forms (60).…”

Section: Discussionmentioning

confidence: 99%

Expression of NAG-1, a Transforming Growth Factor-β Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1

Baek

Kim

Nixon

et al. 2004

Journal of Biological Chemistry

133

116

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Egr-1 inhibits apoptosis during the UV response: correlation of cell survival with Egr-1 phosphorylation

Cited by 61 publications

References 32 publications

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

In Vivo Cloning and Characterization of a New Growth Suppressor Protein TOE1 as a Direct Target Gene of Egr1

Expression of NAG-1, a Transforming Growth Factor-β Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1

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