Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues.
NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described. NOX4 mRNA expression, as shown by real-time PCR, was present in normal thyroid tissue, regulated by TSH and significantly increased in differentiated cancer tissues. TSH increased the protein level of NOX4 in human thyroid primary culture and NOX4-dependent ROS generation. NOX4 immunostaining was detected in normal and pathologic thyroid tissues. In normal thyroid tissue, staining was heterogeneous and mostly found in activated columnar thyrocytes but absent in quiescent flat cells. Papillary and follicular thyroid carcinomas displayed more homogeneous staining. The p22(phox) protein that forms a heterodimeric enzyme complex with NOX4 displayed an identical cellular expression pattern and was also positively regulated by TSH. ROS may have various biological effects, depending on the site of production. Intracellular NOX4-p22(phox) localization suggests a role in cytoplasmic redox signaling, in contrast to the DUOX localization at the apical membrane that corresponds to an extracellular H(2)O(2) production. Increased NOX4-p22(phox) in cancer might be related to a higher proliferation rate and tumor progression but a role in the development of tumors has to be further studied and established in the future.
CNRS, FRE2939, Villejuif F-94805, France.
Urbain
U
Weyemi
Bernard
B
Caillou
Monique
M
Talbot
Rabii
R
Ameziane-El-Hassani
Ludovic
L
Lacroix
Odile
O
Lagent-Chevallier
Abir
A
Al Ghuzlan
Dirk
D
Roos
Jean-Michel
JM
Bidart
Alain
A
Virion
Martin
M
Schlumberger
Corinne
C
Dupuy
D018263:Adenocarcinoma, Follicular / Q000201:enzymology* / Q000473:pathology; D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D000074623:Dual Oxidases; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010084:Oxidation-Reduction; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology*; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013972:Thyrotropin; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human; C431513:DUOX1 protein, human