Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

Parra, Eduardo; Ferreira, Jorge; Ortega, Arnaldo

doi:10.3892/ijo.2011.1047

Cited by 20 publications

(31 citation statements)

References 35 publications

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“…Our results show that indeed, without an external source of Egr-1, constitutive activation of NF-κB and AP-1 is associated with the expression of Egr-1, as knockdown of Egr-1 expression caused a significant inhibition of NF-κB and AP-1 activity and reduction in p21 and cIAP2 mRNA expression. This corroborates our previous studies that have suggested that forced expression of Egr-1 in PC-3 and LNCaP cells causes constitutive activation of NF-κB and AP-1 (38). The external stimulation of Egr-1 may be advantageous to proliferation, survival, motility and invasion, and resistance to cytotoxic drugs, when surviving in an ectopic environment, such as during seeding and growth in distant organs, such as the bone and lungs.…”

Section: Discussionsupporting

confidence: 79%

“…The phenotype of this inhibition is seen as the cell cycle arrest at the G1 to S-phase transition. This study complements and extends our previous study (38) in which a 5-10-fold increase in Egr-1 mRNA, NF-κB and AP-1 and protein levels in cell culture studies were observed. This compares to our finding that siRNA mediated silencing resulted in >98% reduction in Egr-1 mRNA and 91% reduction in Egr-1 protein in vitro, which led to dramatic changes in the cellular phenotype.…”

Section: Discussionsupporting

confidence: 78%

“…Our previous study demonstrated overexpression of Egr-1 in PC-3 and LNCaP prostate carcinoma cell lines caused pronounced increase in protein levels of NF-κB and AP-1 (38). In this study, we observed that depletion of the endogenous expression of Egr-1 (over 90%) by siRNA decreased PC-3 and LNCaP cell proliferation, cell growth and induced transcriptional arrest of the members of the related NF-κB and AP-1 nuclear factors.…”

Section: Discussionmentioning

confidence: 59%

“…Whether constitutive activation of NF-κB and AP-1 is a cause of Egr-1 production or whether constitutive production of Egr-1 elevates NF-κB and AP-1 activity is not clear. however, at least in PC-3 and LNCaP cells, it was recently elucidated that overexpression of Egr-1 results in increased NF-κB and AP-1 activity during normal and stressed conditions (38). Our results show that indeed, without an external source of Egr-1, constitutive activation of NF-κB and AP-1 is associated with the expression of Egr-1, as knockdown of Egr-1 expression caused a significant inhibition of NF-κB and AP-1 activity and reduction in p21 and cIAP2 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Parra

Ferreira²,

Sáenz³

2011

Int J Mol Med

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Abstract. Previous studies suggest that the effects of Egr-1 on tumorigenesis are critically dependent on the levels of Egr-1 and the cellular context. For this reason, we examined the effects of blocking the Egr-1 activity by a short interfering RNA (siRNA) against Egr-1 on the expression of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling in the PC-3 and LNCaP prostate carcinoma cell lines. We observed that the reduction in expression of Egr-1 in PC-3 and LNCaP cells by effects of the siRNA vector resulted in lower cell viability and increased apoptosis at 24 and 120 h after transfection. This reduced cell viability correlated well with a reduced activity of the NF-κB and AP-1 factors. We analyzed the expression and activity of these factors and found that p65 and IκB but not p50 were reduced in the siRNA-treated cells. Similarly, we found that c-Fos but not c-Jun was reduced in the siRNA treated cells. These effects were translated to reduced transcriptional activity of NF-κB over cellular inhibitor of apoptosis (cIAP) and p21 genes, as assayed by RT-PCR and of AP-1 over a luciferase reporter activated by AP-1 response elements. Egr-1 was also found to interact directly with p65 and IκB members of the NF-κB family, thereby was able to regulate directly their activity by post-transcriptional effects. These results suggest that Egr-1 may promote prostate cancer development by modulating the activity of factors NF-κB and AP-1, which are involved in cell proliferation and apoptosis.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Parra

Ferreira²,

Sáenz³

2011

Int J Mol Med

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“…Membranes were incubated with SAP/JNK, p38 or ERK-1/2 antibody (dilution 1:1,000) and PP4 antibody (dilution 1:1,000) (Santa Cruz Biotechnology). Primary incubation was followed by incubations with HRP-conjugated secondary antibody (1:2,000; NEB), and detection was made with super signal chemiluminescent substrate (31)(32)(33)(34).…”

Section: Plasmid Construction and Preparation Of Nuclear Extractsmentioning

confidence: 99%

Activation of MAP kinase family members triggered by TPA or ionomycin occurs via the protein phosphataseï¿½4 pathway in Jurkat leukemia T cells

Parra

2011

Mol Med Report

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Abstract. Protein phosphatase 4 (PP4) is a protein phosphatase 2A (PP2A)-related, okadaic acid-sensitive, serine/threonine protein phosphatase that shares 65% amino acid identity with PP2A. Numerous studies have shown that protein phosphatase is involved in the regulation of T cell signaling and activation. In this study, we investigated the effect of overexpression of PP4 on the expression of members of the MAP kinase family in Jurkat leukemia T cells, which had previously been stimulated with UV, 12-O-tetradecanoylphorbol-13-acetate (TPA), ionomycin and okadaic acid. We found that the overexpression of PP4 expressed relatively low activity in the absence of any kind of stimulation. However, TPA, UV or ionomycin treatment strongly increased the activity of PP4. In addition, Jurkat T cells, transfected with various expression plasmids and/or stimulated with TPA, UV or ionomycin strongly induced the c-Jun N-terminal kinase (JNK) and p38, whereas the extracellular signal-regulated kinase (ERK)-1/2 kinase pathway was weekly activated. Treatment of Jurkat T cells with okadaic acid, an inhibitor of PP2, also inhibited the increase of JNK and p38 activity induced by PP4. The effect of okadaic acid on the activity of PP4 was similar to that observed in Jurkat T cells treated with a dominant negative c-Jun (dn-jun). These results indicate that the activation of JNK and p38, but not ERKs, is a target for the PP4 activity in Jurkat leukemia T cells.

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TRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma

Hajek

Sewell

Kaech

et al. 2017

Cancer

101

105

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Background The incidence of HPV-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. The number of newly diagnosed HPV+ HNSCC cases in the United States currently outnumber any other HPV-associated cancer, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV+ HNSCC is expected to continue for ~60 years. Compared to tobacco-associated HNSCC, patients with HPV+ HNSCC have better overall survival and higher response to treatment. Current treatment, including chemo- and radiation therapy, is associated with lifelong morbidity, and there are limited treatments and no curative options for patients who develop recurrent metastatic disease. Therapeutic de-escalation (decreased radiation dose) is being tested through clinical trials; however, these studies select patients based solely on tumor and patient smoking characteristics. Mechanisms of HPV-driven carcinogenesis in HNSCC are not well understood, which limits new therapeutic strategies and hinders appropriate selection of patients for de-escalation therapy. Methods We analyzed TCGA HNSCC data to identify molecular characteristics correlating with outcome and integration status of the HPV genome. Results Our studies identified a subset of HPV+ HNSCC with mutations in TRAF3 and CYLD. TRAF3 and CYLD defects correlated with activation of transcriptional factor NF-κB, episomal HPV status of tumors, and improved survival of patients. Conclusions Defects in TRAF3/CYLD were accompanied with activation of NF-κB signaling and maintenance of episomal HPV in tumors, suggesting that these mutations may support an alternative mechanism of HPV tumorigenesis in head and neck tumors.

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Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

Cited by 20 publications

References 35 publications

Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Activation of MAP kinase family members triggered by TPA or ionomycin occurs via the protein phosphataseï¿½4 pathway in Jurkat leukemia T cells

TRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma

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