TY - JOUR
T1 - Oxidative stress in thyroid carcinomas
T2 - Biological and clinical significance
AU - Ameziane El Hassani, Rabii
AU - Buffet, Camille
AU - Leboulleux, Sophie
AU - Dupuy, Corinne
N1 - Publisher Copyright:
© 2019 Society for Endocrinology Published by Bioscientifica Ltd.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - Dedifferentiation
KW - Genetic instability
KW - NADPH oxidase
KW - Oxidative stress
KW - Thyroid
UR - http://www.scopus.com/inward/record.url?scp=85060617047&partnerID=8YFLogxK
U2 - 10.1530/ERC-18-0476
DO - 10.1530/ERC-18-0476
M3 - Review article
C2 - 30615595
AN - SCOPUS:85060617047
SN - 1351-0088
VL - 26
SP - R131-R143
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
IS - 3
ER -