Genomic profiling of C/EBPβ2 transformed mammary epithelial cells: A role for nuclear interleukin-1β

Russell, Alisha; Boone, Braden; Jiang, Aixiang; Sealy, Linda

doi:10.4161/cbt.10.5.12725

Cited by 7 publications

(4 citation statements)

References 36 publications

(39 reference statements)

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“…Similarly, a comparable PTG-driven induction of the transcription factor has been obtained in human monocytes isolated from peripheral blood samples of healthy donors, along with a concomitant induction of IL-1β mRNA expression (Barilli et al, unpublished results). These results are consistent with literature findings stating that C/EBPβ is involved in myeloid development and macrophage activation [25,47], and is a crucial mediator of inflammation in activated macrophages [48], particularly responsible for IL-1β transcription [49]. Our hypothesis is, hence, that this protein could be involved both in the gliadin-dependent activation of arginase pathway in macrophages [16] and, at least in part, in the onset of the inflammatory dysfunction described upon interaction of immune cells with gliadin [50].…”

Section: Discussionsupporting

confidence: 95%

Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro

Barilli

Rotoli

Visigalli

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Celiac disease (CD) is an immune-mediated enteropathy sustained by dietary gluten in susceptible individuals, and characterized by a complex interplay between adaptive and innate responses against gluten peptides (PTG). In a recent contribution we have demonstrated that the treatment with PTG induces the expression and activity of arginase in both murine macrophages and human monocytes from healthy subjects, thus suggesting a role for arginine and its metabolites in gluten-triggered response of these cells. Here we further explore this field, by addressing the effects of PTG on polyamine synthesis and release in murine RAW264.7 macrophages, and how they affect epithelial permeability of Caco-2 monolayers. Results obtained show a massive production and release of putrescine by macrophages upon incubation with gluten peptides; this, in turn, causes a decrease in TEER in epithelial cells, indicating that PTG-driven secretion of polyamines by macrophages has a role in the modulation of intestinal permeability in vitro. At a molecular level, putrescine production appears referable to the activation of C/EBPβ transcription factor, which is known to be responsible for arginase induction in activated macrophages and is a crucial mediator of inflammation. Whether these pathways are stimulated also in vivo deserves to be further investigated, as well as their role in gluten-driven cellular and intestinal defects typical of CD patients.

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Section: Discussionsupporting

confidence: 95%

Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro

Barilli

Rotoli

Visigalli

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Silencing of Par4 markedly promoted CEBPB transcription, and CEBPB could bind to the FAK promoter and enhance its transcription. CEBPB is essential for mammary gland growth and development and has been associated with poor prognosis in breast cancer (Russell et al, 2010;Zahnow, 2009). Overexpression of CEBPB in MCF10A cells was reported to result in EMT and ErbB independence (Russell et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…CEBPB is essential for mammary gland growth and development and has been associated with poor prognosis in breast cancer (Russell et al, 2010;Zahnow, 2009). Overexpression of CEBPB in MCF10A cells was reported to result in EMT and ErbB independence (Russell et al, 2010). FAK has kinase-dependent and kinase-independent scaffolding, cytoplasmic and nuclear functions (Golubovskaya, 2014).…”

Section: Discussionmentioning

confidence: 99%

Expression of microRNA miR-17-3p inhibits mouse cardiac fibroblast senescence by targeting Par4

Li²,

et al. 2014

Journal of Cell Science

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The microRNA miR-17-92 cluster plays a fundamental role in heart development. The aim of this study was to investigate the effect of a member of this cluster, miR-17, on cardiac senescence. We examined the roles of miR-17 in senescence and demonstrated that miR-17-3p attenuates cardiac aging in the myocardium by targeting Par4 (also known as PAWR). This upregulates the downstream proteins CEBPB, FAK, N-cadherin, vimentin, Oct4 and Sca-1 (also known as stem cell antigen-1), and downregulates E-cadherin. Par4 has been reported as a tumor suppressor gene that induces apoptosis in cancer cells, but not in normal cells. Repression of Par4 by miR-17-3p enhances the transcription of CEBPB and FAK, which promotes mouse cardiac fibroblast (MCF) epithelial-tomesenchymal transition (EMT) and self-renewal, resulting in cellular senescence and apoptosis resistance. We conclude that Par4 can bind to the CEBPB promoter and inhibit its transcription. Decreased Par4 expression increases the amount of CEBPB, which binds to the FAK promoter and enhances FAK transcription. Par4, CEBPB and FAK form a senescence signaling pathway, playing roles in modulating cell survival, growth, apoptosis, EMT and self-renewal. Through this novel senescence signaling axis, miR-17-3p represses Par4 expression, acting pleiotropically as a negative modulator of cardiac aging and cardiac fibroblast cellular senescence.

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“…18 additional ras-dependent modifications not shown include p-T109 and pS-111 by unknown kinases and monomethylation of r114 (numbering for rat protein). 18 additional kinases known to phosphorylate C/EBPb include PKa, 31 PKC, 32 p38, 33 Ca 2+ /calmodulin-dependent kinase, 34 and GSK3. 35 To produce the WI-38-hTERT-SV40T/t-Ras cells, serial infections were performed followed by appropriate selection.…”

Section: C/ebpbmentioning

confidence: 99%

C/EBPbeta’s role in determining Ras-induced senescence or transformation

Atwood

Sealy

2011

Small GTPases

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Introduction of activated Ras into normal cells leads to senescence, a tumor suppressive mechanism, whereas expression of this oncogene in many immortalized cell lines leads to transformation. Studying the signaling differences in cells that undergo Ras-induced senescence versus Ras transformation may shed light on potential therapeutic targets in the treatment of cancer. C/EBPβ is a transcription factor necessary for both Ras-induced senescence and Ras transformation. Three isoforms of this transcription factor exist due to alternative translation initation at three in frame ATGs. C/EBPβ1 is the isoform responsible for oncogene-induced senescence, and this isoform is degraded by the proteosome during Ras transformation. Phosphorylation of C/EBPβ1 on Thr235 by Cdk2 is necessary, but not sufficient, for degradation of C/EBPβ1. Proteasomal degradation of C/EBPβ1 may represent a mechanism to evade senescence. In contrast, C/EBPβ2 is expressed in breast cancer cells and is involved in proliferation, supporting a role for this isoform in Ras transformation. We propose here that one potential signaling difference in Ras-induced senescence versus Ras transformation is that Ras signals through different C/EBPβ isoforms (C/EBPβ1 versus C/EBPβ2) during these processes.

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Genomic profiling of C/EBPβ2 transformed mammary epithelial cells: A role for nuclear interleukin-1β

Cited by 7 publications

References 36 publications

Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro

Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro

Expression of microRNA miR-17-3p inhibits mouse cardiac fibroblast senescence by targeting Par4

C/EBPbeta’s role in determining Ras-induced senescence or transformation

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