Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours

Abstract

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/μg 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.