A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role i...
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| Format: | Online |
| Language: | English |
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Impact Journals LLC
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741662/ |
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pubmed-4741662 |
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oai_dc |
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pubmed-47416622016-03-03 A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC Occhi, Gianluca Barollo, Susi Regazzo, Daniela Bertazza, Loris Galuppini, Francesca Guzzardo, Vincenza Jaffrain-Rea, Marie Lise Vianello, Federica Ciato, Denis Ceccato, Filippo Watutantrige-Fernando, Sara Bisognin, Andrea Bortoluzzi, Stefania Pennelli, Gianmaria Boscaro, Marco Scaroni, Carla Mian, Caterina Research Paper The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice. Impact Journals LLC 2015-09-16 /pmc/articles/PMC4741662/ /pubmed/26392334 Text en Copyright: © 2015 Occhi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Occhi, Gianluca Barollo, Susi Regazzo, Daniela Bertazza, Loris Galuppini, Francesca Guzzardo, Vincenza Jaffrain-Rea, Marie Lise Vianello, Federica Ciato, Denis Ceccato, Filippo Watutantrige-Fernando, Sara Bisognin, Andrea Bortoluzzi, Stefania Pennelli, Gianmaria Boscaro, Marco Scaroni, Carla Mian, Caterina |
| spellingShingle |
Occhi, Gianluca Barollo, Susi Regazzo, Daniela Bertazza, Loris Galuppini, Francesca Guzzardo, Vincenza Jaffrain-Rea, Marie Lise Vianello, Federica Ciato, Denis Ceccato, Filippo Watutantrige-Fernando, Sara Bisognin, Andrea Bortoluzzi, Stefania Pennelli, Gianmaria Boscaro, Marco Scaroni, Carla Mian, Caterina A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| author_facet |
Occhi, Gianluca Barollo, Susi Regazzo, Daniela Bertazza, Loris Galuppini, Francesca Guzzardo, Vincenza Jaffrain-Rea, Marie Lise Vianello, Federica Ciato, Denis Ceccato, Filippo Watutantrige-Fernando, Sara Bisognin, Andrea Bortoluzzi, Stefania Pennelli, Gianmaria Boscaro, Marco Scaroni, Carla Mian, Caterina |
| author_sort |
Occhi, Gianluca |
| title |
A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| title_short |
A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| title_full |
A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| title_fullStr |
A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| title_full_unstemmed |
A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC |
| title_sort |
constitutive active mapk/erk pathway due to brafv600e positively regulates ahr pathway in ptc |
| description |
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice. |
| publisher |
Impact Journals LLC |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741662/ |
| _version_ |
1613533850395213824 |