Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies.
<h4>Background</h4>Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While...
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2011
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oai:doaj.org-article:d3a99fb0c6ef4f82a7482ab49f89e9022021-11-18T06:50:42ZSimilar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies.1932-620310.1371/journal.pone.0021589https://doaj.org/article/d3a99fb0c6ef4f82a7482ab49f89e9022011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21754991/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies.<h4>Methodology/principal findings</h4>We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors.<h4>Conclusion/significance</h4>Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα.Martine Perrot-ApplanatSophie VacherAurore ToullecIrma PelaezGuillaume VelascoFrançoise CormierHanan El Sheikh SaadRosette LidereauVéronique BaudIvan BièchePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e21589 (2011) |
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Medicine R Science Q |
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Medicine R Science Q Martine Perrot-Applanat Sophie Vacher Aurore Toullec Irma Pelaez Guillaume Velasco Françoise Cormier Hanan El Sheikh Saad Rosette Lidereau Véronique Baud Ivan Bièche Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| description |
<h4>Background</h4>Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies.<h4>Methodology/principal findings</h4>We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors.<h4>Conclusion/significance</h4>Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα. |
| format |
article |
| author |
Martine Perrot-Applanat Sophie Vacher Aurore Toullec Irma Pelaez Guillaume Velasco Françoise Cormier Hanan El Sheikh Saad Rosette Lidereau Véronique Baud Ivan Bièche |
| author_facet |
Martine Perrot-Applanat Sophie Vacher Aurore Toullec Irma Pelaez Guillaume Velasco Françoise Cormier Hanan El Sheikh Saad Rosette Lidereau Véronique Baud Ivan Bièche |
| author_sort |
Martine Perrot-Applanat |
| title |
Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| title_short |
Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| title_full |
Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| title_fullStr |
Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| title_full_unstemmed |
Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies. |
| title_sort |
similar nf-κb gene signatures in tnf-α treated human endothelial cells and breast tumor biopsies. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/d3a99fb0c6ef4f82a7482ab49f89e902 |
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