A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

Gianluca Occhi, Susi Barollo, Daniela Regazzo, Loris Bertazza, Francesca Galuppini, Vincenza Guzzardo, Marie Lise Jaffrain-Rea, Federica Vianello, Denis Ciato, Filippo Ceccato, Sara Watutantrige-Fernando, Andrea Bisognin, Stefania Bortoluzzi, Gianmaria Pennelli, Marco Boscaro, Carla Scaroni, Caterina Mian

Research output: Contribution to journalArticlepeer-review

Abstract

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 metaanalysis 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.

Original languageEnglish
Pages (from-to)32104-32114
Number of pages11
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - 2015

Keywords

  • Aryl hydrocarbon receptor
  • BRAF
  • Gene expression
  • Meta-analysis
  • Papillary thyroid cancer

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'A constitutive active MAPK/ERK pathway due to BRAF<sup>V600E</sup> positively regulates AHR pathway in PTC'. Together they form a unique fingerprint.

Cite this