Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes.
The expression of 4 thyroid tissue-specific genes [Na+/I- symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R)] as well as of the glucose transporter type 1 (Glut1) gene was analyzed in 90 human thyroid tissues Messenger ribonucleic acids were extracted from 43 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves' thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used. NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves' thyroid tissues (up to 140-fold). TPO expression was decreased in thyroid carcinomas, but was normal in cold adenomas; it was increased in toxic adenomas and Graves' thyroid tissues Tg expression was decreased in thyroid carcinomas, but was normal in the other tissues. TSH-R expression was normal in most tissues studied and was decreased in only some thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, Tg and TSH-R. No relationship was found with the age of the patient. Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01). Expression of the Glut1 gene was increased in 1 of 24 adenomas and in 8 of 43 thyroid carcinomas. In 6 thyroid carcinoma patients, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake. In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential regulation of the expression of thyroid-specific genes; 3) an increased expression of Glut-1 gene in some malignant tumors that may suggest a role for glucose derivative tracers to detect in vivo thyroid cancer metastases by positron emission tomography scanning.
Lazar
V
V
Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
Bidart
J M
JM
Caillou
B
B
Mahé
C
C
Lacroix
L
L
Filetti
S
S
Schlumberger
M
M
D018263:Adenocarcinoma, Follicular / Q000235:genetics; D000236:Adenoma / Q000235:genetics; D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D051272:Glucose Transporter Type 1; D006111:Graves Disease / Q000235:genetics; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011989:Receptors, Thyrotropin / Q000235:genetics; D027981:Symporters; D013954:Thyroglobulin / Q000235:genetics; D013964:Thyroid Neoplasms / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D007453:Iodide Peroxidase; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D027981:Symporters; D013954:Thyroglobulin; D000099209:Sodium-Iodide Symporters; C495677:SLC2A1 protein, human