Tumor Protein p63/Nuclear Factor κB Feedback Loop in Regulation of Cell Death

Sen, Tanusree; Sen, Nilkantha; Huang, Yiping; Sinha, Debasish; Luo, Zhen-Ge; Ratovitski, Edward A.; Sidransky, David

doi:10.1074/jbc.m111.257105

Cited by 14 publications

(12 citation statements)

References 68 publications

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“…29 Thus, p63-induced NF-jB can be pro-or anti-apoptotic, depending on the cellular environment. 28 This case series found no statistically significant difference in NF-jB expression between pcDLBCLL and pcFCLL, although there are multiple alternate NF-jB epitopes not assessed in this study. Nevertheless, all NF-jB positive cases coexpressed p63, and this may represent another mechanism for dysregulation of p63 expression.…”

Section: Discussioncontrasting

confidence: 56%

“…Conversely, a novel anti‐apoptotic pathway in mature B cells has been described in which NF‐κB up‐regulates TAp63 expression that transactivates BCL‐2 gene expression . Thus, p63‐induced NF‐κB can be pro‐ or anti‐apoptotic, depending on the cellular environment . This case series found no statistically significant difference in NF‐κB expression between pcDLBCLL and pcFCLL, although there are multiple alternate NF‐κB epitopes not assessed in this study.…”

Section: Discussioncontrasting

confidence: 52%

“…TAp63 is a regulator of NF-jB transcription and protein stability, leading subsequently to increased susceptibility to cell death in mammary epithelial cells. 28 Conversely, a novel anti-apoptotic pathway in mature B cells has been described in which NF-jB up-regulates TAp63 expression that transactivates BCL-2 gene expression. 29 Thus, p63-induced NF-jB can be pro-or anti-apoptotic, depending on the cellular environment.…”

Section: Discussionmentioning

confidence: 99%

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Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma‐leg type, and is of the TAp63 isoform

et al. 2016

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Section: Discussioncontrasting

confidence: 56%

Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma‐leg type, and is of the TAp63 isoform

et al. 2016

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“…On the other hand, we show that HHK exposed to pepsin produces higher transcriptional levels of Tp63, compared to their corresponding controls but a trend of decreased transcriptional activity at low pH (Fig 5B-a). These data in HHK are supported by the identified inverse correlation between transcriptional levels of Tp63 and RELA(p65) [51], but a significant positive linear correlation to Tp53 with apoptotic function (Fig 6C, 6D, 6E and 6F) [46,52]. …”

Section: Discussionmentioning

confidence: 63%

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

Sasaki¹,

Toman²,

Vageli³

2016

PLoS ONE

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BackgroundExtra-esophageal carcinogenesis has been widely discussed in relation to the chronic effects of laryngopharyngeal reflux and most prominently with pepsin historically central to this discussion. With refluxate known to include gastric (pepsin) and duodenal (bile) fluids, we recently demonstrated the mechanistic role of NF-κB in mediating the preneoplastic effects of acidic-bile. However, the role of pepsin in promoting hypopharyngeal premalignant events remains historically unclear. Here, we investigate the in vitro effect of acidic-pepsin on the NF-κB oncogenic pathway to better define its potential role in hypopharyngeal neoplasia.MethodsHuman hypopharyngeal primary cells (HHPC) and keratinocytes (HHK) were repetitively exposed to physiologic pepsin concentrations (0.1 mg/ml) at pH 4.0, 5.0 and 7.0. Cellular localization of phospho-NF-κB and bcl-2 was determined using immunofluorescence and western blotting. NF-κB transcriptional activity was tested by luc reporter and qPCR. Analysis of DNA content of pepsin treated HHK and HHPC was performed using Fluorescence-activated-cell sorting assay. To explore a possible dose related effect, pepsin concentration was reduced from 0.1 to 0.05 and 0.01 mg/ml.ResultsAt physiologic concentration, acidic-pepsin (0.1 mg/ml at pH 4.0) is lethal to most normal hypopharyngeal cells. However, in surviving cells, no NF-κB transcriptional activity is noted. Acidic-pepsin fails to activate the NF-κB or bcl-2, TNF-α, EGFR, STAT3, and wnt5α but increases the Tp53 mRNAs, in both HHPC and HHK. Weakly acidic-pepsin (pH 5.0) and neutral-pepsin (pH 7.0) induce mild activation of NF-κB with increase in TNF-α mRNAs, without oncogenic transcriptional activity. Lower concentrations of pepsin at varying pH do not produce NF-κB activity or transcriptional activation of the analyzed genes.ConclusionOur findings in vitro do not support the role of acidic-pepsin in NF-κB related hypopharyngeal carcinogenesis.

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“…TAp63 isoforms acted as tumor suppressors by regulating senescence through p53-independent pathways (25), whereas ∆Np63 isoforms enhance proliferation and inhibit apoptosis (26,27). A recent report showed that TAp63 regulates NF-κB transcription and protein stability, subsequently leading to the cell death phenotype (28). Another report showed TAp63 is a transcriptional target of NF-κB, which may play a role in cell proliferation, differentiation and survival upon NF-κB activation (29,30).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells

Funamizu

Lacy

Parpart

et al. 2014

International Journal of Oncology

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Recent studies have demonstrated that deregulated microRNA (miR) expression is implicated in the development of human cancers. In the aberrant miR expression, miR-301 is upregulated in cancers, such as pancreatic, colorectal and oral carcinoma. Based on this evidence, we investigated the contribution of miR-301 to pancreatic carcinoma and the novel target genes of miR-301 in pancreatic carcinoma. In this study, we analyzed the effects of enforced and inhibited expression of miR-301b expression in the Panc-1 and BxPC-3 cell lines. MiR-301b expression levels were associated with cell invasiveness in both cell lines. Additional experiments indicated that miR-301b influences invasiveness through CDH1. Moreover microRNA target search algorithms and experimental strategies suggested that miR-301b suppressed TP63 expression as a novel target of miR-301b. Remarkably, miR-301b was also found to be associated with NF-κB activity in both cell lines. In summary, overexpressed miR-301b may suppress TP63 expression and contributes to promote cell invasiveness and to enhance gemcitabine resistance in pancreatic carcinoma cells. Thus, miR-301b may have potential as a novel therapeutic target for cancer treatment due to its stimulatory effects on cell invasiveness.

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Tumor Protein p63/Nuclear Factor κB Feedback Loop in Regulation of Cell Death

Cited by 14 publications

References 68 publications

Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma‐leg type, and is of the TAp63 isoform

Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma‐leg type, and is of the TAp63 isoform

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells

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