Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas.
Duox2, and probably Duox1 are glycoflavoproteins involved in the thyroid H2O2 generator functionally associated to thyroperoxidase (TPO). We investigated both DUOX1 and DUOX2 gene expressions using quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 47 thyroid carcinomas, including 10 paired normal/tumoral tissues. In carcinomas, variations of DUOX1 and DUOX2 mRNA levels were parallel, indicating that control mechanisms of both gene expressions operate in tumors as well as in normal thyroid tissues; DUOX1 expression was in the normal range in 20, was decreased up to 50-fold in 8, and increased up to 7-fold in 19 samples. DUOX2 expression was in the normal range in 15, was decreased up to 200-fold in 10, and increased up to 5-fold in 22 samples. In the 10 paired samples, variations of DUOX and TPO gene expressions were not correlated. We analyzed Duoxl/2 protein expression in 86 tumor samples using an antipeptide antiserum reacting with both Duox proteins. In normal tissue, Duox proteins are localized at the apical pole of thyrocytes, with 40% to 60% of thyrocytes being stained. In the 86 cancer tissues, immunostaining was absent in 19 samples, was low in 32, and normal or even slightly increased in the other 35 samples. The expression of Duox proteins was related to tumor differentiation, being more frequently found in neoplastic tissues that were able to pick up radioiodine, and in those with a detectable expression of sodium iodide symporter (NIS), pendrin and TPO.
Lacroix
L
L
Department of Clinical Biology, Institut Gustave-Roussy, Villejuif, France.
Nocera
M
M
Mian
C
C
Caillou
B
B
Virion
A
A
Dupuy
C
C
Filetti
S
S
Bidart
J M
JM
Schlumberger
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism*; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D000074623:Dual Oxidases; D005260:Female; D005420:Flavoproteins; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000096:biosynthesis; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D000074623:Dual Oxidases; D005420:Flavoproteins; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C431513:DUOX1 protein, human