NF-κB Mediates the Expression of TBX15 in Cancer Cells
TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human ca...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915632/ https://www.ncbi.nlm.nih.gov/pubmed/27327083 http://dx.doi.org/10.1371/journal.pone.0157761 |
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author | Arribas, Jéssica Cajuso, Tatiana Rodio, Angela Marcos, Ricard Leonardi, Antonio Velázquez, Antonia |
author_facet | Arribas, Jéssica Cajuso, Tatiana Rodio, Angela Marcos, Ricard Leonardi, Antonio Velázquez, Antonia |
author_sort | Arribas, Jéssica |
collection | PubMed |
description | TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human cancer cells, by analyzing the regulatory function of a 5’-distal conserved region of TBX15. Bisulfite sequencing showed high methylation of the CpG island contained in this region that was not correlated with TBX15 mRNA levels, in the cancer cell lines analyzed; however, after 5-aza-dC treatment of TPC-1 cells an increase of TBX15 expression was observed. We also found a significant response of TBX15 to TNF-α activation of the NF-κB pathway using five cancer cell lines, and similar results were obtained when NF-κB was activated with PMA/ionomycin. Next, by luciferase reporter assays, we identified the TBX15 regulatory region containing two functional NF-κB binding sites with response to NF-κBp65, mapping on the -3302 and -3059 positions of the TBX15 gene. Moreover, a direct interaction of NF-κBp65 with one of the two NF-κB binding sites was indicated by ChIP assays. In summary, we provide novel data showing that NF-κB signaling up-regulates TBX15 expression in cancer cells. Furthermore, the link between TBX15 and NF-κB found in this study may be important to understand cancer and development processes. |
format | Online Article Text |
id | pubmed-4915632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49156322016-07-06 NF-κB Mediates the Expression of TBX15 in Cancer Cells Arribas, Jéssica Cajuso, Tatiana Rodio, Angela Marcos, Ricard Leonardi, Antonio Velázquez, Antonia PLoS One Research Article TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human cancer cells, by analyzing the regulatory function of a 5’-distal conserved region of TBX15. Bisulfite sequencing showed high methylation of the CpG island contained in this region that was not correlated with TBX15 mRNA levels, in the cancer cell lines analyzed; however, after 5-aza-dC treatment of TPC-1 cells an increase of TBX15 expression was observed. We also found a significant response of TBX15 to TNF-α activation of the NF-κB pathway using five cancer cell lines, and similar results were obtained when NF-κB was activated with PMA/ionomycin. Next, by luciferase reporter assays, we identified the TBX15 regulatory region containing two functional NF-κB binding sites with response to NF-κBp65, mapping on the -3302 and -3059 positions of the TBX15 gene. Moreover, a direct interaction of NF-κBp65 with one of the two NF-κB binding sites was indicated by ChIP assays. In summary, we provide novel data showing that NF-κB signaling up-regulates TBX15 expression in cancer cells. Furthermore, the link between TBX15 and NF-κB found in this study may be important to understand cancer and development processes. Public Library of Science 2016-06-21 /pmc/articles/PMC4915632/ /pubmed/27327083 http://dx.doi.org/10.1371/journal.pone.0157761 Text en © 2016 Arribas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Arribas, Jéssica Cajuso, Tatiana Rodio, Angela Marcos, Ricard Leonardi, Antonio Velázquez, Antonia NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title | NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title_full | NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title_fullStr | NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title_full_unstemmed | NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title_short | NF-κB Mediates the Expression of TBX15 in Cancer Cells |
title_sort | nf-κb mediates the expression of tbx15 in cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915632/ https://www.ncbi.nlm.nih.gov/pubmed/27327083 http://dx.doi.org/10.1371/journal.pone.0157761 |
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