Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours.
OBJECTIVE
Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported. The expression of the NIS gene is up-regulated by TSH through the cAMP pathway and the characterization of the promoter region of the rat NIS gene revealed the existence of a degenerate cAMP response element (CRE) sequence. The cAMP-dependent transcription factor cAMP response element-binding protein (CREB) binds to CRE acting, upon phosphorylation, as a transcriptional activator. In this study we evaluated the expression of CREB and NIS gene in thyroid non-functioning adenomas (n=18) and carcinomas (n=20), as well as in the corresponding normal tissue.


METHODS
The levels of CREB and NIS mRNA were determined by quantitative real-time RT-PCR, whereas CREB protein (total and phosphorylated) was analyzed by Western blot.


RESULTS
The levels of CREB mRNA in thyroid carcinomas, but not in adenomas, were significantly lower than in the corresponding normal tissue (4.63+/-0.89 vs 9.51+/-2.01 pg/microg total RNA, means+/-s.e., P=0.025). CREB protein levels, which were determined in a subset of samples, were in quite good agreement with mRNA data. NIS mRNA levels did not differ in adenomas or carcinomas, compared with the corresponding normal tissue and no significant relationship with the levels of CREB mRNA was observed.


CONCLUSIONS
Our results have indicated for the first time that reduced levels of CREB expression are a feature of thyroid carcinomas, and confirm that different factors are likely to modulate NIS expression.
Endocrine Unit, Departm,ent of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Paola
P
Luciani
Lisa
L
Buci
Barbara
B
Conforti
Massimo
M
Tonacchera
Patrizia
P
Agretti
Rossella
R
Elisei
Agnese
A
Vivaldi
Federica
F
Cioppi
Giancarlo
G
Biliotti
Giuseppe
G
Manca
Paolo
P
Vitti
Mario
M
Serio
Alessandro
A
Peri
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters