Oxidative stress in thyroid carcinomas: Biological and clinical significance

Rabii Ameziane El Hassani, Camille Buffet, Sophie Leboulleux, Corinne Dupuy

Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

82 Citations (Scopus)

Résumé

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H 2 O 2 , are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability. Indeed, one particularity of this organ is that follicular thyroid cells synthesise thyroid hormones through a complex mechanism that requires H 2 O 2 . Because of their detection in thyroid adenomas and in early cell transformation, both oxidative stress and DNA damage are believed to be neoplasia-preceding events in thyroid cells. Oxidative DNA damage is, in addition, detected in the advanced stages of thyroid cancer, suggesting that oxidative lesions of DNA also contribute to the maintenance of genomic instability during the subsequent phases of tumourigenesis. Finally, ionizing radiation and the mutation of oncogenes, such as RAS and BRAF, play a key role in thyroid carcinogenesis through separate and unique mechanisms: they upregulate the expression of two distinct 'professional' ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, which cause DNA damage that may promote chromosomal instability, tumourigenesis and dedifferentiation.

langue originaleAnglais
Pages (de - à)R131-R143
journalEndocrine-Related Cancer
Volume26
Numéro de publication3
Les DOIs
étatPublié - 1 mars 2019
Modification externeOui

Contient cette citation